Testosterone deficiency reduces the effects of late cardiac remodeling after acute myocardial infarction in rats

Abstract

Testosterone is associated with an increased risk of coronary heart disease. This study evaluated cardiac remodeling 60 days after myocardial infarction (MI) in rats with testosterone deficiency. One week after castration, the animals underwent myocardial infarction. Rats were divided into four groups: orchidectomized (OCT); orchidectomized and infarcted (OCT+MI), MI and control (Sham). The myocyte cross-sectional area and the papillary muscle contractility were evaluated 8 weeks after MI. The coronary bed was perfused with Biodur E20 resin to evaluate the neovascularization after MI. Data were expressed as mean ± SEM followed by ANOVA. Castration reduced myocyte hypertrophy when compared to Sham and myocardial infarction alone as well as preserved the contraction force and activation time after myocardial infarction. After beta-adrenergic stimulation, activation and relaxation kinetics were less impaired in the OCT+MI group than in the MI group. Contraction force was preserved in the OCT+MI group after beta-adrenergic stimulation. Multiple scanning electronic microscope images were obtained to characterize changes in the coronary arteries. Capillary density index was increased in the MI and OCT+MI groups compared with control. The MI and OCT+MI groups were characterized by irregular vessel arrangements with distorted shape, abrupt changes in vessel direction, as well as abrupt changes in diameter after bifurcations when compared to Sham and OCT. The results indicated that testosterone deficiency attenuates adverse cardiac remodeling after MI. Novel findings in this study were that testosterone deficiency in rats, induced by castration, changes the later remodeling after MI, when compared with non castrated rats. The absence of this androgenous hormone seems to be benefic against pathological hypertrophy.

Over-expression of microRNA-145 drives alterations in β-adrenergic signaling and attenuates cardiac remodeling in heart failure post myocardial infarction

“…Weight gain of lung and heart are characteristics of advanced HF [13][14][15]. As shown in Table 1, HFinduced augments in lung weight (LW) and heart weight (HW) were reflected by the increase in LW/BW and HW/BW ratio respectively.…”

Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement

“…Thus, the cardiac muscle phenotype can directly be regulated by androgenic steroids. The use of anabolic steroids (as synthetic derivatives of the male sex hormones testosterone), for example, was also shown to be associated with cardiac hypertrophy in both, human and animals ( 24 ) and low levels of DHT are described to be protective against cardiac hypertrophy ( 25 ).…”

Testosterone, cardiomyopathies, and heart failure

“…In another study, testosterone deficiency induced by orchidectomy in rats was shown to alter the pattern of late remodeling postinfarction, with a lower degree of pathological cardiac hypertrophy and an improvement in contractile parameters. 107 …”

“…The main effect of testosterone on post-MI remodeling may occur in myocytes, mainly through the induction of hypertrophy via androgen receptors 108 and increased apoptosis. 107 In humans with heart failure post-MI, the rates of myocyte necrosis and apoptosis are higher in men than in women, and these differences are associated with the earlier onset of the disease in males than in females. 109 …”