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Abstract

The present study was undertaken to determine the effects of AT1 receptor blockade which occurred in response to losartan, on the extracellular matrix (ECM) degradation process in the Bio 14.6 (n = 12) and Bio 53.58 (n = 12) strains which are referred as models of hypertrophic and dilated cardiomyopathy, respectively. The administration of losartan (30 mg/kg/day) in hamsters from 10-20 weeks of age reduced the accumulation of the left ventricular collagen matrix in both of the Bio 14.6 and the Bio 53.58 strains. According to the RT-PCR, the levels of mRNA for matrix metalloproteinase (MMP) and the tissue inhibitor of MMP (TIMP) were examined. MMP-1, -2, -3, and -9 were more enhanced in both myopathic strains than in the control F1beta, strains. With losartan, the levels of MMP-1, -2, -9, TIMP-1 and -2 decreased in the both strains but those for MMP-3 did not in Bio 14.6 strains. TIMP-3 and -4 mRNA levels did not change in any of the experimental hamsters, whether treated or untreated with losartan. The Western blots also showed similar observations in the both strains as seen in mRNA expressions although MMP-2 in the Bio 53.58 strains did not differ between treated and untreated with losartan. Although losartan has an inhibitory effect on collagen accumulation in the development of cardiomyopathy, MMPs (-1, -2, -9) and TIMPs (-1, -2) seem to be susceptible to responding to losartan in Bio cardiomyopathic hamsters.

Metalloproteinases and Hypertrophic Cardiomyopathy: A Systematic Review

“…Four trials that met our inclusion criteria were excluded after review of the full manuscript ( supplemental material ) because they were animal research [ 26 , 27 , 28 , 29 ].…”

Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review

“…In patients with the genetic predisposition to develop non-hypertrophic cardiomyopathy (NHCM) but no structural changes or symptoms, it has been suggested that the use of RAAS blockade may be more beneficial than when it is used in patients with left ventricular fibrosis and hypertrophy who have the genetic predisposition to HCM, which supports the hypothesis that ARBs can inhibit gene expression and reduce left ventricular mass in NHCMs [ 9 , 13 , 18 ]. In addition to their effects, different studies have shown that using ARBs and ACE inhibitors is safe [ 14 , 16 , 17 ].…”

Regeneration in heart disease—Is ECM the key?

“…Briefly, all ECM components are deposited in larger amounts leading to extensive myocardial fibrosis (Weber 1989). Studies using volume or pressure overload models of heart failure suggest that gene expression of ECM components is largely reversed following treatment with beta-blockers, ACE inhibitors or Angiotensin II receptor blockers (Champetier et al 2009; Grimm et al 2001; Grimm et al 1998; Masutomo et al 2001). The orientation of ECM proteins also changes following an insult.…”