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A H Schmaier - One of the best experts on this subject based on the ideXlab platform.
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assembly activation and physiologic influence of the plasma Kallikrein Kinin System
International Immunopharmacology, 2008Co-Authors: A H SchmaierAbstract:The plasma Kallikrein/Kinin System that consists of the proteins factor XII, preKallikrein, and high molecular weight Kininogen was first recognized as a surface-activated coagulation System arising when blood or plasma interacts with artificial surfaces. Although surface-activated contact activation occurs in vivo when various negatively charged surfaces become exposed, including a developing platelet thrombus, a physiologic, non-injury mechanism for activation, regulation, and function of this System has been elusive. Recent investigations have shown that there is a physiologic pathway for assembly and activation of this System independent of factor XII. Gene deficient mice of the bradyKinin B2 receptor and factor XII have been recognized to have reduced risk for arterial thrombosis. This plasma proteolytic System influences arterial thrombosis independent of influencing hemostasis. Thus, the plasma Kallikrein/Kinin System has two mechanisms for its activation: one that is dependent and another independent of factor XII. Better understanding of this System may lead to insight into mechanisms for arterial thrombosis, independent of hemostasis.
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Assembly, activation, and physiologic influence of the plasma Kallikrein/Kinin System.
International immunopharmacology, 2007Co-Authors: A H SchmaierAbstract:The plasma Kallikrein/Kinin System that consists of the proteins factor XII, preKallikrein, and high molecular weight Kininogen was first recognized as a surface-activated coagulation System arising when blood or plasma interacts with artificial surfaces. Although surface-activated contact activation occurs in vivo when various negatively charged surfaces become exposed, including a developing platelet thrombus, a physiologic, non-injury mechanism for activation, regulation, and function of this System has been elusive. Recent investigations have shown that there is a physiologic pathway for assembly and activation of this System independent of factor XII. Gene deficient mice of the bradyKinin B2 receptor and factor XII have been recognized to have reduced risk for arterial thrombosis. This plasma proteolytic System influences arterial thrombosis independent of influencing hemostasis. Thus, the plasma Kallikrein/Kinin System has two mechanisms for its activation: one that is dependent and another independent of factor XII. Better understanding of this System may lead to insight into mechanisms for arterial thrombosis, independent of hemostasis.
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assembly and activation of the plasma Kallikrein Kinin System a new interpretation
International Immunopharmacology, 2002Co-Authors: Zia Shariatmadar, Fakhri Mahdi, A H SchmaierAbstract:Abstract Understanding the importance and physiologic activity of the plasma Kallikrein/Kinin System (KKS) has been thwarted by the absence of an inclusive theory for its assembly and activation. The contact activation hypothesis describes the assembly and activation of this System in test tubes and disease states, but not under physiologic circumstances. Recent investigations have indicated a new cohesive hypothesis for understanding physiologic activation of this System. PreKallikrein (PK) and factor XI (FXI) through high molecular weight Kininogen (HK) assemble on a co-localized, multiprotein receptor complex on endothelial cells that consists of at least cytokeratin 1 (CK1), gC1qR, and urokinase plasminogen activator receptor (uPAR). When assembled on these proteins, preKallikrein becomes activated to Kallikrein by the membrane-expressed enzyme prolylcarboxypeptidase (PRCP). Formed Kallikrein then activates factor XII (FXII) for amplification of its activation and single chain urokinase. The plasma Kallikrein/Kinin System may serve as a physiologic counterbalance to the plasma renin angiotensin System (RAS) by lowering blood pressure and preventing thrombosis. Insights into the integrated role of these two Systems may afford the development of novel therapeutic drugs to manage hypertension and thrombosis.
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activation of the plasma Kallikrein Kinin System on endothelial cell membranes
Immunopharmacology, 1999Co-Authors: R Røjkjaer, A H SchmaierAbstract:Abstract For more than three decades, it has been known that the plasma Kallikrein/Kinin System becomes activated when exposed to artificial, negatively charged surfaces. The existence of an encompassing in vivo, negatively charged surface capable of activation of the plasma Kallikrein/Kinin System has, however, never been convincingly demonstrated. In this report, we describe current knowledge on how the proteins of the plasma Kallikrein/Kinin System assemble to become activated on cell membranes. On endothelial cells, the activation of the plasma Kallikrein/Kinin System is not initiated by factor XII autoactivation as seen on artificial surfaces. On endothelial cells, preKallikrein is activated by an antipain sensitive protease. PreKallikrein activation is dependent on the presence of high molecular weight Kininogen and an optimal free Zn 2+ concentration. Kallikrein generated on the surface of endothelial cell is capable of activating factor XII. Further, Kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight Kininogen, liberating bradyKinin and the HK·PK complex from the endothelial cell surface. Endothelial cell-associated Kallikrein also is capable of kinetically favorable pro-urokinase and, subsequent, plasminogen activation.
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activation of the plasma Kallikrein Kinin System on cells a revised hypothesis
Thrombosis and Haemostasis, 1999Co-Authors: A H Schmaier, R Røjkjaer, Zia ShariatmadarAbstract:Introduction: For the last 25 years, most investigators in the field of plasma Kallikrein/Kinin have accepted the contact activation hypothesis by factor XII initiates plasma Kallikrein/Kinin System activation by binding to a physiologic, negatively-charged surface. This hypothesis forms the basis of the common surface-based coagulation assays, such as the activated partial thromboplastin time (aPTT). Also, it may be the mechanism by which the plasma Kallikrein/Kinin System becomes activated in vivo when exposed to artificial surfaces, such as those used in medical interventions, and following infection. A physiologic, negatively-charged surface, however, capable of initiating the activation of this System has never been convincingly described. This fact questions the role of this System in vivo. Sulfatides, phospholipids, cholesterol sulfate, chondroitin sulfate, heparins, and other glycosaminoglycans have been proposed as physiologic negatively charged surfaces. The autoactivation of factor XII, which can take several hours depending on the surface, leads to preKallikrein (PK) activation. Kallikrein formation reciprocally activates more factor XII in a reaction that is at least 1,000-fold faster than autoactivation. In addition to the surface, the rate of initiation and amplification of this System is accelerated by high molecular weight Kininogen (HK). Activation of the zymogens factor XII and PK result in enzymes that have been proposed to contribute to factor XI activation (coagulation), complement activation, bradyKinin (BK) liberation, fibrinolysis, and granulocyte activation in vitro. It is well known, however, that clinical deficiencies in factor XII, PK, and HK are not associated with bleeding, even though these deficiencies markedly prolong surfaced-activated coagulation assays for hemostasis. This information indicates that this System contributes little, if anything, to hemostasis. Recently, this field has been thoroughly reviewed.1,2 The purpose of this report is to present a new hypothesis for assembly and activation of this System on viable cell membranes and to begin to clarify these proteins’ roles in vivo. Over 10 years ago, our laboratory developed a working hypothesis to serve as an alternative to the factor XII autoactivation mechanism for the initiation of activation of the proteins of the plasma Kallikrein/Kinin System. We reasoned that, in vivo, it is the assembly of a multiprotein complex of these proteins on cell receptors that allows for localization and activation of this System. To prove that hypothesis, we sought to accomplish the following three things. First, we attempted to determine whether there is a receptor(s) for the proteins of this System on cell membranes. Second, we sought to show whether the assembly of the proteins of the plasma Kallikrein/Kinin System on cell membranes results in activation of PK and factor XII. Finally, we attempted to demonstrate biological activities associated with the activation of these proteins on cell membranes. The following report details this work and characterizes a new hypothesis for the assembly and activation of the proteins of the plasma Kallikrein/Kinin System.
Robert W. Colman - One of the best experts on this subject based on the ideXlab platform.
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Kallikrein-Kinin System in Postgastrectomy Dumping Syndrome
2016Co-Authors: Guy G. Raymond, Robert W. ColmanAbstract:The Kallikrein-Kinin System was studied in 10 postgastrectomy patients, 5 with the dumping syndrome and 5 patients without symptoms. After drinking 220 ml of 4 5 % glucose, none of the asymptomatic patients developed symptoms of the dumping syndrome, elevated levels of bradyKinin, or preKallikrein activation; the mean blood pressure fall was not significant. The symptomatic group had headaches, lightheadedness, diarrhea, and a significantly decreased mean blood pressure of 19.4%. A rise in plasma bradyKinin levels to above normal occurred in all patients. Two had activation of plasma Kallikrein, manifested by a drop in preKallikrein and complete disappearance of Kallikrein inhibitor; one of these two also had increased free Kallikrein, shown by Kinin release from Kininogen. The mechanism of Kinin release in the othe
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fifty years of research on the plasma Kallikrein Kinin System from protein structure and function to cell biology and in vivo pathophysiology
Thrombosis and Haemostasis, 2007Co-Authors: Irma M Sainz, Robin A Pixley, Robert W. ColmanAbstract:Fifty years of research on the plasma Kallikrein-Kinin System: From protein structure and function to cell biology and in-vivo pathophysiology -
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Kallikrein Kinin System activation in crohn s disease differences in intestinal and Systemic markers
The American Journal of Gastroenterology, 2002Co-Authors: Massimo Devani, Massimo Cugno, M Vecchi, Stefano Ferrero, Federica Di Berardino, Ettore Contessini Avesani, Roberto De Franchis, Robert W. ColmanAbstract:Kallikrein-Kinin System activation in Crohn's disease: differences in intestinal and Systemic markers
Makoto Katori - One of the best experts on this subject based on the ideXlab platform.
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A role of the renal Kallikrein-Kinin System in the kidney.
Acta physiologica Hungarica, 2008Co-Authors: Makoto Katori, Masataka MajimaAbstract:Makoto Katori and Masataka Majima: A role of the renal Kallikrein-Kinin System\ud in the kidney | Kenneth D. Mitchell: Response to ‘A role of the Kallikrein-Kinin\ud System in the kidney
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Roles of the Renal Kallikrein-Kinin System in Salt-Sensitive Hypertension
Hypertension (Dallas Tex. : 1979), 2004Co-Authors: Makoto Katori, Masataka MajimaAbstract:To the Editor: We read with great interest the review article “Dietary Sodium and Blood Pressure” by Dr Daniel W. Jones in Hypertension ,1 which gives an excellent overview of the present status of the relationship between sodium intake and blood pressure increase. It is, however, a pity that this review did not mention the roles of the renal Kallikrein-Kinin System in the kidney. On the basis of ample evidence, we believe that the renal Kallikrein-Kinin System plays an important role in the excretion of “extra sodium,”2 as follows: 1. The renal Kallikrein-Kinin System has a unique localization. After the tubulo-glomerular feedback System has completed its role …
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Role of the renal Kallikrein-Kinin System in the development of salt-sensitive hypertension
Biological chemistry, 2001Co-Authors: Makoto Katori, Masataka Majima, Izumi Hayashi, Tomoe Fujita, Mariko YamanakaAbstract:The role of the renal Kallikrein-Kinin System in the development of salt-sensitive hypertension was studied using mutant Kininogen-deficient Brown-Norway Katholiek (BN-Ka) rats, which generate no Kinin in their urine, and other hypertensive rat models. It was found that ingestion of a low sodium diet or infusion of NaCl in doses slightly above 0.15 M caused hypertension and sodium accumulation in erythrocytes and the cerebrospinal fluid of Kininogen-deficient BN-Ka rats. Development of hypertension in the deoxycorticosterone-acetate-salt model was completely prevented by administration of a newly discovered inhibitor, ebelactone B, of carboxypeptidase Y-like exopeptidase (an urinary Kininase). The urinary Kallikrein excretion of spontaneously hypertensive rats was lower than that of Wistar Kyoto rats at 4 weeks of age and did not increase by administration of furosemide, a diuretic agent, although approximately 50% of the diuretic action of this agent was dependent upon the renal Kallikrein-Kinin System in normal rats. In conclusion, the renal Kallikrein-Kinin System works as a safety valve for excess sodium intake.
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pivotal role of renal Kallikrein Kinin System in the development of hypertension and approaches to new drugs based on this relationship
Japanese Journal of Pharmacology, 1996Co-Authors: Makoto Katori, Masataka MajimaAbstract:Abstract. Renal Kallikrein is one of the tissue Kallikreins, and the distal nephron is fully equipped as an element of the Kallikrein-Kinin System. Although a low excretion of urinary Kallikrein has been reported in essential hypertension, the results from studies on patients with hypertension are not consistent. Congenitally hypertensive animals also excrete lowered levels of urinary Kallikrein, but the effects of this are yet unknown. Extensive genetic and environmental studies on large Utah pedigrees suggest that the causes of hypertension are closely related to the combination of low Kallikrein excretion and the potassium intake. Mutant Kininogen-deficient Brown Norway-Katholiek rats, which cannot generate Kinin in the urine, are very sensitive to salt loading and to sodium retention by aldosterone released by a non-pressor dose of angiotensin II, which results in hypertension. The major function of renal Kallikrein-Kinin System is to excrete sodium and water when excess sodium is present in the body. Failure of this function causes accumulation of sodium in the cerebrospinal fluid and erythrocytes, and probably in the vascular smooth muscle, which become sensitive to vasoconstrictors. We hypothesize that impaired function of the renal Kallikrein-Kinin System may play a pivotal role in the early development of hypertension. Inhibitors of Kinin degradation in renal tubules and agents, which accelerate the secretion of urinary Kallikrein from the connecting tubules and increase the generation of urinary Kinin, may be novel drugs against hypertension.
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Approaches to the development of novel antihypertensive drugs: crucial role of the renal Kallikrein-Kinin System.
Trends in pharmacological sciences, 1995Co-Authors: Masataka Majima, Makoto KatoriAbstract:The renal Kallikrein-Kinin System has been shown to be important in the development of hypertension, but its precise role remains to be determined. The recent use of mutant rats that are deficient in plasma Kininogens and hence incapable of generating Kinin in the renal tubules has facilitated elucidation of the involvement of Kinin in hypertension. In this article, Masataka Majima and Makoto Katori provide evidence that the renal Kallikrein-Kinin System plays a crucial role in the development of hypertension and discuss a novel rationale for developing effective new antihypertensive drugs.
Masataka Majima - One of the best experts on this subject based on the ideXlab platform.
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A role of the renal Kallikrein-Kinin System in the kidney.
Acta physiologica Hungarica, 2008Co-Authors: Makoto Katori, Masataka MajimaAbstract:Makoto Katori and Masataka Majima: A role of the renal Kallikrein-Kinin System\ud in the kidney | Kenneth D. Mitchell: Response to ‘A role of the Kallikrein-Kinin\ud System in the kidney
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Roles of the Renal Kallikrein-Kinin System in Salt-Sensitive Hypertension
Hypertension (Dallas Tex. : 1979), 2004Co-Authors: Makoto Katori, Masataka MajimaAbstract:To the Editor: We read with great interest the review article “Dietary Sodium and Blood Pressure” by Dr Daniel W. Jones in Hypertension ,1 which gives an excellent overview of the present status of the relationship between sodium intake and blood pressure increase. It is, however, a pity that this review did not mention the roles of the renal Kallikrein-Kinin System in the kidney. On the basis of ample evidence, we believe that the renal Kallikrein-Kinin System plays an important role in the excretion of “extra sodium,”2 as follows: 1. The renal Kallikrein-Kinin System has a unique localization. After the tubulo-glomerular feedback System has completed its role …
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Role of the renal Kallikrein-Kinin System in the development of salt-sensitive hypertension
Biological chemistry, 2001Co-Authors: Makoto Katori, Masataka Majima, Izumi Hayashi, Tomoe Fujita, Mariko YamanakaAbstract:The role of the renal Kallikrein-Kinin System in the development of salt-sensitive hypertension was studied using mutant Kininogen-deficient Brown-Norway Katholiek (BN-Ka) rats, which generate no Kinin in their urine, and other hypertensive rat models. It was found that ingestion of a low sodium diet or infusion of NaCl in doses slightly above 0.15 M caused hypertension and sodium accumulation in erythrocytes and the cerebrospinal fluid of Kininogen-deficient BN-Ka rats. Development of hypertension in the deoxycorticosterone-acetate-salt model was completely prevented by administration of a newly discovered inhibitor, ebelactone B, of carboxypeptidase Y-like exopeptidase (an urinary Kininase). The urinary Kallikrein excretion of spontaneously hypertensive rats was lower than that of Wistar Kyoto rats at 4 weeks of age and did not increase by administration of furosemide, a diuretic agent, although approximately 50% of the diuretic action of this agent was dependent upon the renal Kallikrein-Kinin System in normal rats. In conclusion, the renal Kallikrein-Kinin System works as a safety valve for excess sodium intake.
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pivotal role of renal Kallikrein Kinin System in the development of hypertension and approaches to new drugs based on this relationship
Japanese Journal of Pharmacology, 1996Co-Authors: Makoto Katori, Masataka MajimaAbstract:Abstract. Renal Kallikrein is one of the tissue Kallikreins, and the distal nephron is fully equipped as an element of the Kallikrein-Kinin System. Although a low excretion of urinary Kallikrein has been reported in essential hypertension, the results from studies on patients with hypertension are not consistent. Congenitally hypertensive animals also excrete lowered levels of urinary Kallikrein, but the effects of this are yet unknown. Extensive genetic and environmental studies on large Utah pedigrees suggest that the causes of hypertension are closely related to the combination of low Kallikrein excretion and the potassium intake. Mutant Kininogen-deficient Brown Norway-Katholiek rats, which cannot generate Kinin in the urine, are very sensitive to salt loading and to sodium retention by aldosterone released by a non-pressor dose of angiotensin II, which results in hypertension. The major function of renal Kallikrein-Kinin System is to excrete sodium and water when excess sodium is present in the body. Failure of this function causes accumulation of sodium in the cerebrospinal fluid and erythrocytes, and probably in the vascular smooth muscle, which become sensitive to vasoconstrictors. We hypothesize that impaired function of the renal Kallikrein-Kinin System may play a pivotal role in the early development of hypertension. Inhibitors of Kinin degradation in renal tubules and agents, which accelerate the secretion of urinary Kallikrein from the connecting tubules and increase the generation of urinary Kinin, may be novel drugs against hypertension.
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Approaches to the development of novel antihypertensive drugs: crucial role of the renal Kallikrein-Kinin System.
Trends in pharmacological sciences, 1995Co-Authors: Masataka Majima, Makoto KatoriAbstract:The renal Kallikrein-Kinin System has been shown to be important in the development of hypertension, but its precise role remains to be determined. The recent use of mutant rats that are deficient in plasma Kininogens and hence incapable of generating Kinin in the renal tubules has facilitated elucidation of the involvement of Kinin in hypertension. In this article, Masataka Majima and Makoto Katori provide evidence that the renal Kallikrein-Kinin System plays a crucial role in the development of hypertension and discuss a novel rationale for developing effective new antihypertensive drugs.
Carsten Tschöpe - One of the best experts on this subject based on the ideXlab platform.
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New perspective on the tissue Kallikrein-Kinin System in myocardial infarction: role of angiogenesis and cardiac regeneration.
International immunopharmacology, 2007Co-Authors: Dirk Westermann, Heinz-peter Schultheiss, Carsten TschöpeAbstract:An intensification of the local cardiac Kallikrein-Kinin System (KKS) is thought to delay the development of cardiac failure. Since myocardial infarction is one of the leading causes of death in the developed countries, the role of the Kallikrein-Kinin System was studied in numerous experimental studies focusing on this disease using strategies like Kallikrein gene transfer, tissue Kallikrein infusion and/or by use of human Kallikrein over expressing animals. These studies suggested that the Kallikrein-Kinin System increases coronary blood flow, decreases infarct size and left ventricular remodeling post myocardial infarction. This is of special interest since pharmacological inhibition of the angiotensin converting enzyme acts not only by reducing angiotensin II levels, but also by preventing enzymatic breakdown of Kinins, suggesting that the Kallikrein-Kinin System is part of ACE inhibition effects. Here we review the current concept of the Kallikrein-Kinin System during myocardial infarction with special regard to its effects on angiogenesis and myocardial regeneration.
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The role of the renal Kallikrein-Kinin System in diabetic nephropathy.
Current opinion in nephrology and hypertension, 2007Co-Authors: Alexander Riad, Jia Long Zhuo, Heinz-peter Schultheiss, Carsten TschöpeAbstract:Diabetic nephropathy is one of the most common complications in diabetes mellitus. Multiple pathogenic mechanisms are now believed to contribute to this disease, including inflammatory cytokines, autacoids and oxidative stress. Numerous studies have shown that the Kallikrein-Kinin System may be involved in these mechanisms. This review focuses on recent research advance on the potential role of the Kallikrein-Kinin System in the development of diabetic nephropathy, and its clinical relevance. A collection of recent studies has shown that angiotensin-converting enzyme inhibitors, which inhibit angiotensin II formation and degradation of bradyKinin, and vasopeptidase inhibitors attenuated the development of diabetic nephropathy in experimental animals and clinical settings. The role of the Kallikrein-Kinin System in diabetes is further supported by findings that diabetic nephropathy is worsened in diabetic mice lacking bradyKinin B2 receptors. Although long-acting bradyKinin B2 receptor agonists have been shown to have renal protective effects, their therapeutic benefits have not been well studied. Current experimental investigations demonstrated that pharmacological intervention of the Kallikrein-Kinin System improved renal conditions in diabetes mellitus. These findings suggest that the Kallikrein-Kinin System may be a therapeutic target in preventing and treating diabetic nephropathy.
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the role of the renal Kallikrein Kinin System in diabetic nephropathy
Current Opinion in Nephrology and Hypertension, 2007Co-Authors: Alexander Riad, Jia Long Zhuo, Heinz-peter Schultheiss, Carsten TschöpeAbstract:Purpose of review Diabetic nephropathy is one of the most common complications in diabetes mellitus. Multiple pathogenic mechanisms are now believed to contribute to this disease, including inflammatory cytokines, autacoids and oxidative stress. Numerous studies have shown that the Kallikrein–Kinin System may be involved in these mechanisms. This review focuses on recent research advance on the potential role of the Kallikrein–Kinin System in the development of diabetic nephropathy, and its clinical relevance.
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Cardioprotective mechanisms of the Kallikrein–Kinin System in diabetic cardiopathy
Current opinion in nephrology and hypertension, 2006Co-Authors: Frank Spillmann, Heinz-peter Schultheiss, Sophie Van Linthout, Carsten TschöpeAbstract:Purpose of reviewMultiple pathogenic mechanisms contribute to the development of diabetic cardiopathy, including intramyocardial inflammation, cardiac fibrosis, abnormal intracellular Ca2+ handling, microangiopathy and endothelial dysfunction. Moreover, the cardiac Kallikrein–Kinin System is thought
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cardioprotective mechanisms of the Kallikrein Kinin System in diabetic cardiopathy
Current Opinion in Nephrology and Hypertension, 2006Co-Authors: Frank Spillmann, Heinz-peter Schultheiss, Sophie Van Linthout, Carsten TschöpeAbstract:Purpose of reviewMultiple pathogenic mechanisms contribute to the development of diabetic cardiopathy, including intramyocardial inflammation, cardiac fibrosis, abnormal intracellular Ca2+ handling, microangiopathy and endothelial dysfunction. Moreover, the cardiac Kallikrein–Kinin System is thought
