Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Transforming growth factor-beta blockade down-regulates the renin-angiotensin system and modifies cardiac remodeling after myocardial infarction Ellmers LJ; Scott NJ; Medicherla S; Pilbrow AP; Bridgman PG; Yandle TG; Richards AM; Protter AA; Cameron VAEndocrinology 2008[Nov]; 149 (11): 5828-34After myocardial infarction (MI), the heart may undergo progressive ventricular remodeling, resulting in a deterioration of cardiac function. TGF-beta is a key cytokine that both initiates and terminates tissue repair, and its sustained production underlies the development of tissue fibrosis, particularly after MI. We investigated the effects of a novel orally active specific inhibitor of the TGF-beta receptor 1 (SD-208) in an experimental model of MI. Mice underwent ligation of the left coronary artery to induce MI and were subsequently treated for 30 d after infarction with either SD-208 or a vehicle control. Blockade of TGF-beta signaling reduced mean arterial pressure in all groups. SD-208 treatment after MI resulted in a trend for reduced ventricular and renal gene expression of TGF-beta-activated kinase-1 (a downstream modulator of TGF-beta signaling) and a significant decrease in collagen 1, in association with a marked decrease in cardiac mass. Post-MI SD-208 treatment significantly reduced circulating levels of plasma renin activity as well as down-regulating the components of the cardiac and renal renin-angiotensin system (angiotensinogen, angiotensin converting enzyme, and angiotensin II type I receptor). Our findings indicate that blockade of the TGF-beta signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction.|Animals[MESH]|Cardiomegaly/genetics/metabolism/pathology[MESH]|Down-Regulation/drug effects[MESH]|Drug Evaluation, Preclinical[MESH]|Gene Expression Regulation/drug effects[MESH]|Heart/drug effects[MESH]|Kidney/drug effects/metabolism/pathology[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Myocardial Infarction/drug therapy/metabolism/*physiopathology[MESH]|Myocardium/metabolism/pathology[MESH]|Pteridines/*pharmacology/therapeutic use[MESH]|Receptors, Transforming Growth Factor beta/antagonists & inhibitors[MESH]|Renin-Angiotensin System/*drug effects/physiology[MESH]|Renin/blood/metabolism[MESH]|Transforming Growth Factor beta/*antagonists & inhibitors/physiology[MESH]|Ventricular Remodeling/*drug effects[MESH] |