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K. Parekh - One of the best experts on this subject based on the ideXlab platform.
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The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
Experimental Diabetes Research, 2018Co-Authors: F. C. Howarth, K. Parekh, Pychadathil Jayaprakash, Murat Oz, Halina Dobrzynski, M. A. Qureshi, T. E. AdrianAbstract:Background. In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), CACNA1H (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cavγ4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.
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contractility of ventricular myocytes is well preserved despite altered mechanisms of ca2 transport and a changing pattern of mrna in aged type 2 zucker diabetic fatty rat heart
Molecular and Cellular Biochemistry, 2012Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Haider Raza, Ernest Adeghate, Anne John, Thomas E AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca2+ signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca2+ transient were unaltered; however, TPK Ca2+ transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca2+ current was reduced across a wide range of test potentials (−30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca2+ content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca2+ channels, and cell membrane ion transport and intracellular Ca2+ transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, CACNA1H, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca2+ transport and a changing pattern of genes encoding a variety of Ca2+ signalling and cardiac muscle proteins in aged ZDF rat.
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Ventricular myocyte contraction, intracellular calcium and expression of genes encoding cardiac muscle proteins in young and aging Zucker diabetic fatty rat heart reviewed
Hamdan Medical Journal, 2012Co-Authors: Frank Christopher Howarth, K. Parekh, Muhammad Anwar Qureshi, Zahra Hassan, Lina T. Al Kury, Dmytro Isaev, Salem R. R. K. D. Yammahi, Annie John, Haider RazaAbstract:Diabetes mellitus and its complications is a serious global health problem and the total number of people with this disease is projected to rise from 171 million in 2000 to 366 million in 2030. A recent study among Emirati citizens reported age-standardized rates for diabetes mellitus (diagnosed and undiagnosed) and pre-diabetes in those 30–64 years old as 29.0% and 24.2%, respectively. The association between type 2 diabetes mellitus and obesity is very strong and cardiovascular disease is the leading cause of morbidity and mortality among diabetic patients. The changes in ventricular myocyte contraction, intracellular calcium and the expression of genes encoding cardiac muscle proteins that take place in young (9–13 weeks) and ageing (30–34 weeks) Zucker diabetic fatty (ZDF) rat heart have been reviewed. Diabetes mellitus was associated with a fourfold elevation in non-fasting blood glucose in young and ageing ZDF rat compared with age-matched Zucker lean controls. Amplitude of shortening was unaltered in myocytes from young and ageing ZDF rats. Time to peak and time to half relaxation of shortening was prolonged in myocytes from young ZDF rats and was unaltered in myocytes from ageing ZDF rats compared with controls. Amplitude of the Ca2+ transient was unaltered in myocytes from young and ageing ZDF rats. Time to peak Ca2+ transient was prolonged in myocytes from young and ageing ZDF rats. L-type Ca2+ current was significantly reduced in myocytes from young and ageing ZDF rats. Sarcoplasmic reticulum Ca2+ transport did not appear to be altered in myocytes from young or ageing ZDF rats. Expression of genes encoding L-type Ca2+ channel proteins, plasma membrane transporters, sarcoplasmic reticulum Ca2+ and regulatory proteins and cardiac muscle proteins were variously up-regulated, down-regulated or unaltered in ventricles from young and ageing ZDF rats. Up-regulated genes in young ZDF rat heart included CACNA1C , CACNA1G , CACNA1H , ATP1A1 and MYH7 , whereas down-regulated genes in young ZDF rat heart included ATP1B1, SLC9A1 , ATP2A2 , CALM1 , MYH6 , MYL2 , ACTC1 , TNNI3 , TNNT2 and TNNC1 . Up-regulated genes in ageing ZDF rat heart included CACNA1G , CACNA1H , ATP2A1 and MYL2 , whereas down-regulated genes in ageing ZDF rat heart included CACNA2D3 , SLC9A1 , ATP2A2 , MYH6 and TNNT2 . Subtle changes in expression of genes encoding various cardiac muscle proteins may underlie functional changes in hearts
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changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of ca2 signalling in young type 2 zucker diabetic fatty rat heart
Experimental Physiology, 2011Co-Authors: F. C. Howarth, K. Parekh, Murat Oz, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Salem R. R. K. D. Yammahi, Al L Kury, Thomas E Adrian, Ernest AdeghateAbstract:The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca2+ transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca2+ transient was unaltered; however, time-to-peak Ca2+ transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca2+ current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca2+ current was 1.19 ± 0.28 pA pF−1 in ZDF myocytes compared with 2.42 ± 0.40 pA pF−1 in control myocytes. Sarcoplasmic reticulum Ca2+ content, release and uptake and myofilament sensitivity to Ca2+ were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca2+ channel proteins (Cacna1c, Cacna1g, CACNA1H and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca2+ transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca2+ channel proteins might partly underlie alterations in the time course of contraction and Ca2+ transients in ventricular myocytes from ZDF rats.
F. C. Howarth - One of the best experts on this subject based on the ideXlab platform.
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The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
Experimental Diabetes Research, 2018Co-Authors: F. C. Howarth, K. Parekh, Pychadathil Jayaprakash, Murat Oz, Halina Dobrzynski, M. A. Qureshi, T. E. AdrianAbstract:Background. In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), CACNA1H (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cavγ4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.
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contractility of ventricular myocytes is well preserved despite altered mechanisms of ca2 transport and a changing pattern of mrna in aged type 2 zucker diabetic fatty rat heart
Molecular and Cellular Biochemistry, 2012Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Haider Raza, Ernest Adeghate, Anne John, Thomas E AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca2+ signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca2+ transient were unaltered; however, TPK Ca2+ transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca2+ current was reduced across a wide range of test potentials (−30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca2+ content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca2+ channels, and cell membrane ion transport and intracellular Ca2+ transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, CACNA1H, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca2+ transport and a changing pattern of genes encoding a variety of Ca2+ signalling and cardiac muscle proteins in aged ZDF rat.
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changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of ca2 signalling in young type 2 zucker diabetic fatty rat heart
Experimental Physiology, 2011Co-Authors: F. C. Howarth, K. Parekh, Murat Oz, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Salem R. R. K. D. Yammahi, Al L Kury, Thomas E Adrian, Ernest AdeghateAbstract:The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca2+ transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca2+ transient was unaltered; however, time-to-peak Ca2+ transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca2+ current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca2+ current was 1.19 ± 0.28 pA pF−1 in ZDF myocytes compared with 2.42 ± 0.40 pA pF−1 in control myocytes. Sarcoplasmic reticulum Ca2+ content, release and uptake and myofilament sensitivity to Ca2+ were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca2+ channel proteins (Cacna1c, Cacna1g, CACNA1H and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca2+ transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca2+ channel proteins might partly underlie alterations in the time course of contraction and Ca2+ transients in ventricular myocytes from ZDF rats.
Dmytro Isaev - One of the best experts on this subject based on the ideXlab platform.
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contractility of ventricular myocytes is well preserved despite altered mechanisms of ca2 transport and a changing pattern of mrna in aged type 2 zucker diabetic fatty rat heart
Molecular and Cellular Biochemistry, 2012Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Haider Raza, Ernest Adeghate, Anne John, Thomas E AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca2+ signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca2+ transient were unaltered; however, TPK Ca2+ transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca2+ current was reduced across a wide range of test potentials (−30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca2+ content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca2+ channels, and cell membrane ion transport and intracellular Ca2+ transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, CACNA1H, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca2+ transport and a changing pattern of genes encoding a variety of Ca2+ signalling and cardiac muscle proteins in aged ZDF rat.
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Ventricular myocyte contraction, intracellular calcium and expression of genes encoding cardiac muscle proteins in young and aging Zucker diabetic fatty rat heart reviewed
Hamdan Medical Journal, 2012Co-Authors: Frank Christopher Howarth, K. Parekh, Muhammad Anwar Qureshi, Zahra Hassan, Lina T. Al Kury, Dmytro Isaev, Salem R. R. K. D. Yammahi, Annie John, Haider RazaAbstract:Diabetes mellitus and its complications is a serious global health problem and the total number of people with this disease is projected to rise from 171 million in 2000 to 366 million in 2030. A recent study among Emirati citizens reported age-standardized rates for diabetes mellitus (diagnosed and undiagnosed) and pre-diabetes in those 30–64 years old as 29.0% and 24.2%, respectively. The association between type 2 diabetes mellitus and obesity is very strong and cardiovascular disease is the leading cause of morbidity and mortality among diabetic patients. The changes in ventricular myocyte contraction, intracellular calcium and the expression of genes encoding cardiac muscle proteins that take place in young (9–13 weeks) and ageing (30–34 weeks) Zucker diabetic fatty (ZDF) rat heart have been reviewed. Diabetes mellitus was associated with a fourfold elevation in non-fasting blood glucose in young and ageing ZDF rat compared with age-matched Zucker lean controls. Amplitude of shortening was unaltered in myocytes from young and ageing ZDF rats. Time to peak and time to half relaxation of shortening was prolonged in myocytes from young ZDF rats and was unaltered in myocytes from ageing ZDF rats compared with controls. Amplitude of the Ca2+ transient was unaltered in myocytes from young and ageing ZDF rats. Time to peak Ca2+ transient was prolonged in myocytes from young and ageing ZDF rats. L-type Ca2+ current was significantly reduced in myocytes from young and ageing ZDF rats. Sarcoplasmic reticulum Ca2+ transport did not appear to be altered in myocytes from young or ageing ZDF rats. Expression of genes encoding L-type Ca2+ channel proteins, plasma membrane transporters, sarcoplasmic reticulum Ca2+ and regulatory proteins and cardiac muscle proteins were variously up-regulated, down-regulated or unaltered in ventricles from young and ageing ZDF rats. Up-regulated genes in young ZDF rat heart included CACNA1C , CACNA1G , CACNA1H , ATP1A1 and MYH7 , whereas down-regulated genes in young ZDF rat heart included ATP1B1, SLC9A1 , ATP2A2 , CALM1 , MYH6 , MYL2 , ACTC1 , TNNI3 , TNNT2 and TNNC1 . Up-regulated genes in ageing ZDF rat heart included CACNA1G , CACNA1H , ATP2A1 and MYL2 , whereas down-regulated genes in ageing ZDF rat heart included CACNA2D3 , SLC9A1 , ATP2A2 , MYH6 and TNNT2 . Subtle changes in expression of genes encoding various cardiac muscle proteins may underlie functional changes in hearts
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changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of ca2 signalling in young type 2 zucker diabetic fatty rat heart
Experimental Physiology, 2011Co-Authors: F. C. Howarth, K. Parekh, Murat Oz, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Salem R. R. K. D. Yammahi, Al L Kury, Thomas E Adrian, Ernest AdeghateAbstract:The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca2+ transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca2+ transient was unaltered; however, time-to-peak Ca2+ transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca2+ current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca2+ current was 1.19 ± 0.28 pA pF−1 in ZDF myocytes compared with 2.42 ± 0.40 pA pF−1 in control myocytes. Sarcoplasmic reticulum Ca2+ content, release and uptake and myofilament sensitivity to Ca2+ were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca2+ channel proteins (Cacna1c, Cacna1g, CACNA1H and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca2+ transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca2+ channel proteins might partly underlie alterations in the time course of contraction and Ca2+ transients in ventricular myocytes from ZDF rats.
Zahra Hassan - One of the best experts on this subject based on the ideXlab platform.
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contractility of ventricular myocytes is well preserved despite altered mechanisms of ca2 transport and a changing pattern of mrna in aged type 2 zucker diabetic fatty rat heart
Molecular and Cellular Biochemistry, 2012Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Haider Raza, Ernest Adeghate, Anne John, Thomas E AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca2+ signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca2+ transient were unaltered; however, TPK Ca2+ transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca2+ current was reduced across a wide range of test potentials (−30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca2+ content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca2+ channels, and cell membrane ion transport and intracellular Ca2+ transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, CACNA1H, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca2+ transport and a changing pattern of genes encoding a variety of Ca2+ signalling and cardiac muscle proteins in aged ZDF rat.
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Ventricular myocyte contraction, intracellular calcium and expression of genes encoding cardiac muscle proteins in young and aging Zucker diabetic fatty rat heart reviewed
Hamdan Medical Journal, 2012Co-Authors: Frank Christopher Howarth, K. Parekh, Muhammad Anwar Qureshi, Zahra Hassan, Lina T. Al Kury, Dmytro Isaev, Salem R. R. K. D. Yammahi, Annie John, Haider RazaAbstract:Diabetes mellitus and its complications is a serious global health problem and the total number of people with this disease is projected to rise from 171 million in 2000 to 366 million in 2030. A recent study among Emirati citizens reported age-standardized rates for diabetes mellitus (diagnosed and undiagnosed) and pre-diabetes in those 30–64 years old as 29.0% and 24.2%, respectively. The association between type 2 diabetes mellitus and obesity is very strong and cardiovascular disease is the leading cause of morbidity and mortality among diabetic patients. The changes in ventricular myocyte contraction, intracellular calcium and the expression of genes encoding cardiac muscle proteins that take place in young (9–13 weeks) and ageing (30–34 weeks) Zucker diabetic fatty (ZDF) rat heart have been reviewed. Diabetes mellitus was associated with a fourfold elevation in non-fasting blood glucose in young and ageing ZDF rat compared with age-matched Zucker lean controls. Amplitude of shortening was unaltered in myocytes from young and ageing ZDF rats. Time to peak and time to half relaxation of shortening was prolonged in myocytes from young ZDF rats and was unaltered in myocytes from ageing ZDF rats compared with controls. Amplitude of the Ca2+ transient was unaltered in myocytes from young and ageing ZDF rats. Time to peak Ca2+ transient was prolonged in myocytes from young and ageing ZDF rats. L-type Ca2+ current was significantly reduced in myocytes from young and ageing ZDF rats. Sarcoplasmic reticulum Ca2+ transport did not appear to be altered in myocytes from young or ageing ZDF rats. Expression of genes encoding L-type Ca2+ channel proteins, plasma membrane transporters, sarcoplasmic reticulum Ca2+ and regulatory proteins and cardiac muscle proteins were variously up-regulated, down-regulated or unaltered in ventricles from young and ageing ZDF rats. Up-regulated genes in young ZDF rat heart included CACNA1C , CACNA1G , CACNA1H , ATP1A1 and MYH7 , whereas down-regulated genes in young ZDF rat heart included ATP1B1, SLC9A1 , ATP2A2 , CALM1 , MYH6 , MYL2 , ACTC1 , TNNI3 , TNNT2 and TNNC1 . Up-regulated genes in ageing ZDF rat heart included CACNA1G , CACNA1H , ATP2A1 and MYL2 , whereas down-regulated genes in ageing ZDF rat heart included CACNA2D3 , SLC9A1 , ATP2A2 , MYH6 and TNNT2 . Subtle changes in expression of genes encoding various cardiac muscle proteins may underlie functional changes in hearts
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changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of ca2 signalling in young type 2 zucker diabetic fatty rat heart
Experimental Physiology, 2011Co-Authors: F. C. Howarth, K. Parekh, Murat Oz, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Salem R. R. K. D. Yammahi, Al L Kury, Thomas E Adrian, Ernest AdeghateAbstract:The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca2+ transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca2+ transient was unaltered; however, time-to-peak Ca2+ transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca2+ current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca2+ current was 1.19 ± 0.28 pA pF−1 in ZDF myocytes compared with 2.42 ± 0.40 pA pF−1 in control myocytes. Sarcoplasmic reticulum Ca2+ content, release and uptake and myofilament sensitivity to Ca2+ were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca2+ channel proteins (Cacna1c, Cacna1g, CACNA1H and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca2+ transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca2+ channel proteins might partly underlie alterations in the time course of contraction and Ca2+ transients in ventricular myocytes from ZDF rats.
Ernest Adeghate - One of the best experts on this subject based on the ideXlab platform.
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contractility of ventricular myocytes is well preserved despite altered mechanisms of ca2 transport and a changing pattern of mrna in aged type 2 zucker diabetic fatty rat heart
Molecular and Cellular Biochemistry, 2012Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Haider Raza, Ernest Adeghate, Anne John, Thomas E AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca2+ signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca2+ transient were unaltered; however, TPK Ca2+ transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca2+ current was reduced across a wide range of test potentials (−30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca2+ content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca2+ channels, and cell membrane ion transport and intracellular Ca2+ transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, CACNA1H, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca2+ transport and a changing pattern of genes encoding a variety of Ca2+ signalling and cardiac muscle proteins in aged ZDF rat.
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changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of ca2 signalling in young type 2 zucker diabetic fatty rat heart
Experimental Physiology, 2011Co-Authors: F. C. Howarth, K. Parekh, Murat Oz, M. A. Qureshi, Zahra Hassan, Dmytro Isaev, Salem R. R. K. D. Yammahi, Al L Kury, Thomas E Adrian, Ernest AdeghateAbstract:The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca2+ transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca2+ transient was unaltered; however, time-to-peak Ca2+ transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca2+ current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca2+ current was 1.19 ± 0.28 pA pF−1 in ZDF myocytes compared with 2.42 ± 0.40 pA pF−1 in control myocytes. Sarcoplasmic reticulum Ca2+ content, release and uptake and myofilament sensitivity to Ca2+ were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca2+ channel proteins (Cacna1c, Cacna1g, CACNA1H and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca2+ transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca2+ channel proteins might partly underlie alterations in the time course of contraction and Ca2+ transients in ventricular myocytes from ZDF rats.
