Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats

Abstract

Hyperhomocysteinemia (Hhe), linked to cardiovascular disease by epidemiological studies, may be an important factor in adverse cardiac remodeling in hypertension. Specifically, convergence of myocardial and vascular alterations promoted by Hhe and hypertension may exacerbate cardiac remodeling and myocardial dysfunction. We studied male spontaneously hypertensive rats fed one of three diets: control, intermediate Hhe inducing, or severe Hhe inducing. After 10 wk of dietary intervention, cardiac function was assessed in vitro, and cardiac and coronary arteriolar remodeling were monitored by histomorphometric, immunohistochemical, and biochemical techniques. Results showed that Hhe induced diastolic dysfunction, as characterized by the diastolic pressure-volume curve, without significant changes in baseline systolic function. Perivascular collagen levels were increased by Hhe, and there was an increase in left ventricular hydroxyproline levels. Myocyte size was not affected. Coronary arteriolar wall thickness increased with Hhe due to smooth muscle hyperplasia. Mast cells increased in parallel with Hhe and collagen accumulation. In summary, 10 wk of Hhe caused coronary arteriolar remodeling, myocardial collagen deposition, and diastolic dysfunction in hypertensive rats.

Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic Peptide in Rats

“…A recent study from Korea confirmed this finding (10 ). In animal experiments from the group of Joseph and Kennedy (11,12 ), chronic intermediate HHcy induced cardiac hypertrophy, pathological remodeling (11,13,14 ), and diastolic as well as systolic dysfunction (11,12 ). These findings provide strong evidence for a causal role of HHcy in the pathogenesis of left ventricular dysfunction.…”

Rodent models of heart failure: an updated review

“…Hyperhomocysteinemia has been identified as a causative factor of cardiac stress and dysfunction in both spontaneous hypertensive and normotensive rats [129,130]. In rats, supplementation of diet with homocysteine for 10 weeks produces hyperhomocysteinemia and consequently ventricular dysfunction with compromised systolic and diastolic function [52,130].…”

“…In rats, supplementation of diet with homocysteine for 10 weeks produces hyperhomocysteinemia and consequently ventricular dysfunction with compromised systolic and diastolic function [52,130]. The main factors involved in the development of HF are oxidative stress and inflammatory mediators [129].…”

Can markers of collagen turnover or other biomarkers contribute to the diagnostics of heart failure with normal left ventricular ejection fraction?

“…Our study extends these projects in the analysis of big endothelin (indicator of vascular function and neurohumoral activity) and of homocysteine, cysteine, cysteinylglycine, and glutathione (agents affecting primarily myocardial oxidative stress). These agents are likely to have an impact on the development of myocardial hypertrophy and/or fibrosis 36,37 , two important determinants of LV diastolic dysfunction, and could teoretically contribute to the HFNEF diagnostics. In our study, we demonstrated a significant association of big endothelin, PIIINP, and MMP-2 with the diagnosis of HFNEF.…”