The Experts below are selected from a list of 19602 Experts worldwide ranked by ideXlab platform
Suresh C Tyagi - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition. Materials and Methods To verify this, ascending aortic banding was done in wild type mice to create Pressure Overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls. Results Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls. Conclusion Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained Pressure Overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure.
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reversal of systemic hypertension associated cardiac remodeling in chronic Pressure Overload myocardium by ciglitazone
International Journal of Biological Sciences, 2007Co-Authors: Brooke C Henderson, Neetu Tyagi, Corey L Reynolds, Karni S Moshal, Alexander V Ovechkin, Ganesh K Kartha, Walter E Rodriguez, Suresh C TyagiAbstract:Elevated oxidative stress has been characterized in numerous disorders including systemic hypertension, arterial stiffness, left ventricular hypertrophy (LVH) and heart failure. The peroxisome proliferator activated receptor gamma (PPARγ) ameliorates oxidative stress and LVH. To test the hypothesis that PPARγ decreased LVH and cardiac fibrosis in chronic Pressure Overload, in part, by increasing SOD, eNOS and elastin and decreasing NOX4, MMP and collagen synthesis and degradation, chronic Pressure Overload analogous to systemic hypertension was created in C57BL/6J mice by occluding the abdominal aorta above the kidneys (aortic stenosis-AS). The sham surgery was used as controls. Ciglitazone (CZ, a PPARγ agonist, 4 µg/ml) was administered in drinking water. LV function was measured by M-Mode Echocardiography. We found that PPARγ protein levels were increased by CZ. NOX-4 expression was increased by Pressure-Overload and such an increase was attenuated by CZ. SOD expression was not affected by CZ. Expression of iNOS was induced by Pressure-Overload, and such an increase was inhibited by CZ. Protein levels for MMP2, MMP-9, MMP-13 were induced and TIMP levels were decreased by Pressure-Overload. The CZ mitigated these levels. Collagen synthesis was increased and elastin levels were decreased by Pressure-Overload and CZ ameliorated these changes. Histochemistry showed that CZ inhibited interstitial and perivascular fibrosis. Echocardiography showed that CZ attenuated the systolic and diastolic LV dysfunction induced by Pressure-Overload. These observations suggested that CZ inhibited Pressure-overlaod-induced cardiac remodeling, and inhibition of an induction of NOX4, iNOS, MMP-2/MMP-13 expression and collagen synthesis/degradation may play a role in Pressure-Overload induced cardiac remodeling.
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dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic Pressure Overload in mice
Journal of Experimental Medicine, 2007Co-Authors: Youchun Jiang, Suresh C Tyagi, Corey L Reynolds, Walter E Rodriguez, Chang Xiao, Wenke Feng, Zhanxiang Zhou, John W Eaton, Jack T Saari, James Y KangAbstract:Sustained Pressure Overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses preestablished hypertrophic cardiomyopathy caused by Pressure Overload induced by ascending aortic constriction in a mouse model. The reversal occurs in the continued presence of Pressure Overload. Sustained Pressure Overload leads to decreases in cardiac Cu and vascular endothelial growth factor (VEGF) levels along with suppression of myocardial angiogenesis. Cu supplementation replenishes cardiac Cu, increases VEGF, and promotes angiogenesis. Systemic administration of anti-VEGF antibody blunts Cu regression of hypertrophic cardiomyopathy. In cultured human cardiomyocytes, Cu chelation blocks insulin-like growth factor (IGF)-1– or Cu-stimulated VEGF expression, which is relieved by addition of excess Cu. Both IGF-1 and Cu activate hypoxia-inducible factor (HIF)-1α and HIF-1α gene silencing blocks IGF-1– or Cu-stimulated VEGF expression. HIF-1α coimmunoprecipitates with a Cu chaperone for superoxide dismutase-1 (CCS), and gene silencing of CCS, but not superoxide dismutase-1, prevents IGF-1– or Cu-induced HIF-1α activation and VEGF expression. Therefore, dietary Cu supplementation improves the condition of hypertrophic cardiomyopathy at least in part through CCS-mediated HIF-1α activation of VEGF expression and angiogenesis.
Neetu Tyagi - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition. Materials and Methods To verify this, ascending aortic banding was done in wild type mice to create Pressure Overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls. Results Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls. Conclusion Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained Pressure Overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure.
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reversal of systemic hypertension associated cardiac remodeling in chronic Pressure Overload myocardium by ciglitazone
International Journal of Biological Sciences, 2007Co-Authors: Brooke C Henderson, Neetu Tyagi, Corey L Reynolds, Karni S Moshal, Alexander V Ovechkin, Ganesh K Kartha, Walter E Rodriguez, Suresh C TyagiAbstract:Elevated oxidative stress has been characterized in numerous disorders including systemic hypertension, arterial stiffness, left ventricular hypertrophy (LVH) and heart failure. The peroxisome proliferator activated receptor gamma (PPARγ) ameliorates oxidative stress and LVH. To test the hypothesis that PPARγ decreased LVH and cardiac fibrosis in chronic Pressure Overload, in part, by increasing SOD, eNOS and elastin and decreasing NOX4, MMP and collagen synthesis and degradation, chronic Pressure Overload analogous to systemic hypertension was created in C57BL/6J mice by occluding the abdominal aorta above the kidneys (aortic stenosis-AS). The sham surgery was used as controls. Ciglitazone (CZ, a PPARγ agonist, 4 µg/ml) was administered in drinking water. LV function was measured by M-Mode Echocardiography. We found that PPARγ protein levels were increased by CZ. NOX-4 expression was increased by Pressure-Overload and such an increase was attenuated by CZ. SOD expression was not affected by CZ. Expression of iNOS was induced by Pressure-Overload, and such an increase was inhibited by CZ. Protein levels for MMP2, MMP-9, MMP-13 were induced and TIMP levels were decreased by Pressure-Overload. The CZ mitigated these levels. Collagen synthesis was increased and elastin levels were decreased by Pressure-Overload and CZ ameliorated these changes. Histochemistry showed that CZ inhibited interstitial and perivascular fibrosis. Echocardiography showed that CZ attenuated the systolic and diastolic LV dysfunction induced by Pressure-Overload. These observations suggested that CZ inhibited Pressure-overlaod-induced cardiac remodeling, and inhibition of an induction of NOX4, iNOS, MMP-2/MMP-13 expression and collagen synthesis/degradation may play a role in Pressure-Overload induced cardiac remodeling.
Srikanth Givvimani - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition. Materials and Methods To verify this, ascending aortic banding was done in wild type mice to create Pressure Overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls. Results Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls. Conclusion Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained Pressure Overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure.
Sumanth D. Prabhu - One of the best experts on this subject based on the ideXlab platform.
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Mitoquinone ameliorates Pressure Overload-induced cardiac fibrosis and left ventricular dysfunction in mice.
Redox biology, 2019Co-Authors: Li He, Jiajia Song, Miki Jinno, Aaron J. Rogers, Palaniappan Sethu, Namakkal S. Rajasekaran, Ganesh V. Halade, Sumanth D. PrabhuAbstract:Abstract Increasing evidence indicates that mitochondrial-associated redox signaling contributes to the pathophysiology of heart failure (HF). The mitochondrial-targeted antioxidant, mitoquinone (MitoQ), is capable of modifying mitochondrial signaling and has shown beneficial effects on HF-dependent mitochondrial dysfunction. However, the potential therapeutic impact of MitoQ-based mitochondrial therapies for HF in response to Pressure Overload is reliant upon demonstration of improved cardiac contractile function and suppression of deleterious cardiac remodeling. Using a new (patho)physiologically relevant model of Pressure Overload-induced HF we tested the hypothesis that MitoQ is capable of ameliorating cardiac contractile dysfunction and suppressing fibrosis. To test this C57BL/6J mice were subjected to left ventricular (LV) Pressure Overload by ascending aortic constriction (AAC) followed by MitoQ treatment (2 µmol) for 7 consecutive days. Doppler echocardiography showed that AAC caused severe LV dysfunction and hypertrophic remodeling. MitoQ attenuated Pressure Overload-induced apoptosis, hypertrophic remodeling, fibrosis and LV dysfunction. Profibrogenic transforming growth factor-β1 (TGF-β1) and NADPH oxidase 4 (NOX4, a major modulator of fibrosis related redox signaling) expression increased markedly after AAC. MitoQ blunted TGF-β1 and NOX4 upregulation and the downstream ACC-dependent fibrotic gene expressions. In addition, MitoQ prevented Nrf2 downregulation and activation of TGF-β1-mediated profibrogenic signaling in cardiac fibroblasts (CF). Finally, MitoQ ameliorated the dysregulation of cardiac remodeling-associated long noncoding RNAs (lncRNAs) in AAC myocardium, phenylephrine-treated cardiomyocytes, and TGF-β1-treated CF. The present study demonstrates for the first time that MitoQ improves cardiac hypertrophic remodeling, fibrosis, LV dysfunction and dysregulation of lncRNAs in Pressure Overload hearts, by inhibiting the interplay between TGF-β1 and mitochondrial associated redox signaling.
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Mitoquinone ameliorates Pressure Overload-induced cardiac fibrosis and left ventricular dysfunction in mice
Elsevier, 2019Co-Authors: Kah Yong Goh, Jiajia Song, Miki Jinno, Aaron J. Rogers, Palaniappan Sethu, Namakkal S. Rajasekaran, Ganesh V. Halade, Xiaoguang Liu, Sumanth D. PrabhuAbstract:Increasing evidence indicates that mitochondrial-associated redox signaling contributes to the pathophysiology of heart failure (HF). The mitochondrial-targeted antioxidant, mitoquinone (MitoQ), is capable of modifying mitochondrial signaling and has shown beneficial effects on HF-dependent mitochondrial dysfunction. However, the potential therapeutic impact of MitoQ-based mitochondrial therapies for HF in response to Pressure Overload is reliant upon demonstration of improved cardiac contractile function and suppression of deleterious cardiac remodeling. Using a new (patho)physiologically relevant model of Pressure Overload-induced HF we tested the hypothesis that MitoQ is capable of ameliorating cardiac contractile dysfunction and suppressing fibrosis. To test this C57BL/6J mice were subjected to left ventricular (LV) Pressure Overload by ascending aortic constriction (AAC) followed by MitoQ treatment (2 µmol) for 7 consecutive days. Doppler echocardiography showed that AAC caused severe LV dysfunction and hypertrophic remodeling. MitoQ attenuated Pressure Overload-induced apoptosis, hypertrophic remodeling, fibrosis and LV dysfunction. Profibrogenic transforming growth factor-β1 (TGF-β1) and NADPH oxidase 4 (NOX4, a major modulator of fibrosis related redox signaling) expression increased markedly after AAC. MitoQ blunted TGF-β1 and NOX4 upregulation and the downstream ACC-dependent fibrotic gene expressions. In addition, MitoQ prevented Nrf2 downregulation and activation of TGF-β1-mediated profibrogenic signaling in cardiac fibroblasts (CF). Finally, MitoQ ameliorated the dysregulation of cardiac remodeling-associated long noncoding RNAs (lncRNAs) in AAC myocardium, phenylephrine-treated cardiomyocytes, and TGF-β1-treated CF. The present study demonstrates for the first time that MitoQ improves cardiac hypertrophic remodeling, fibrosis, LV dysfunction and dysregulation of lncRNAs in Pressure Overload hearts, by inhibiting the interplay between TGF-β1 and mitochondrial associated redox signaling. Keywords: Mitoquinone, Redox signaling, Ascending aortic constriction, Cardiac remodeling, IncRN
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ccr2 monocyte derived infiltrating macrophages are required for adverse cardiac remodeling during Pressure Overload
JACC: Basic to Translational Science, 2018Co-Authors: Bindiya Patel, Mohamed Ameen Ismahil, Tariq Hamid, Shyam S Bansal, Gregg Rokosh, Matthias Mack, Sumanth D. PrabhuAbstract:Highlights •Hypothesis: CCR2+ monocyte-derived cardiac macrophages are required for adverse LV remodeling, cardiac T-cell expansion, and the transition to HF following Pressure Overload. •The imposition of Pressure Overload via TAC resulted in the early up-regulation of CCL2, CCL7, and CCL12 chemokines in the LV, increased Ly6ChiCCR2+ monocytes in the blood, and augmented CCR2+ infiltrating macrophages in the heart. •Specific and circumscribed inhibition of CCR2+ monocytes and macrophages early during Pressure Overload reduced pathological hypertrophy, fibrosis, and systolic dysfunction during the late phase of Pressure Overload. •The early expansion of CCR2+ macrophages after Pressure Overload was required for long-term cardiac T-cell expansion. •CCR2+ monocytes/macrophages may represent key targets for immunomodulation to delay or prevent HF in Pressure-Overload states.
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mononuclear phagocytes are dispensable for cardiac remodeling in established Pressure Overload heart failure
PLOS ONE, 2017Co-Authors: Bindiya Patel, Mohamed Ameen Ismahil, Tariq Hamid, Shyam S Bansal, Sumanth D. PrabhuAbstract:Background Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in Pressure-Overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in Pressure-Overload heart failure (HF), and that MP depletion would ameliorate remodeling.
Charu Munjal - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition.
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mitochondrial division mitophagy inhibitor mdivi ameliorates Pressure Overload induced heart failure
PLOS ONE, 2012Co-Authors: Srikanth Givvimani, Charu Munjal, Neetu Tyagi, Utpal Sen, Naira Metreveli, Suresh C TyagiAbstract:Background We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during Pressure Overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the Pressure Overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a Pressure Overload heart and thus ameliorates heart failure condition. Materials and Methods To verify this, ascending aortic banding was done in wild type mice to create Pressure Overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls. Results Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls. Conclusion Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained Pressure Overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure.
