Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats

Abstract

A recent report indicated that hyperhomocysteinemia (Hhe), in addition to its atherothrombotic effects, exacerbates the adverse cardiac remodeling seen in response to hypertension, a powerful stimulus for pathological ventricular hypertrophy. The present study was undertaken to determine whether Hhe has a direct effect on ventricular remodeling and function in the absence of other hypertrophic stimuli. Male Wistar-Kyoto rats were fed either an amino acid-defined control diet or an intermediate Hhe-inducing diet. After 10 wk of dietary treatment, rats were subjected to echocardiographic assessment of left ventricular (LV) dimensions and systolic function. Subsequently, blood was collected for plasma homocysteine measurements, and the rats were killed for histomorphometric and biochemical assessment of cardiac remodeling and for in vitro cardiac function studies. Significant LV hypertrophy was detected by echocardiographic measurements, and in vitro results showed hypertrophy with significantly increased myocyte size in the LV and right ventricle (RV). LV and RV remodeling was characterized by a disproportionate increase in perivascular and interstitial collagen, coronary arteriolar wall thickening, and myocardial mast cell infiltration. In vitro study of LV function demonstrated abnormal diastolic function secondary to decreased compliance because the rate of relaxation did not differ between groups. LV systolic function did not vary between groups in vitro. In summary, in the absence of other hypertrophic stimuli short-term intermediate Hhe caused pathological hypertrophy and remodeling of both ventricles with diastolic dysfunction of the LV. These results demonstrate that Hhe has direct adverse effects on cardiac structure and function, which may represent a novel direct link between Hhe and cardiovascular morbidity and mortality, independent of other risk factors.

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].…”

Organotypic tissue culture investigation of homocysteine thiolactone cardiotoxic effect

“…A putative reason for cardiac remodelling upon homocysteine action could be an increase in the number of mast cells which release mediators inducing cardiomyocytal hypertrophy, cell death or fibrosis (4,10). Application of the organotypic tissue culture method made it possible to estimate the direct influence of homocysteine thiolactone on a cardiac tissue cell community.…”

The Role of Mast Cells in Cardiac Diseases and Surgery: Invited Commentary

“…[42][43][44] Hem kli nik hem de prek li nik ça lış ma lar da, kar di yak hi per tro fi ile de hi per ho mo sis te i ne mi arasın da po zi tif bir iliş ki bu lun muş tur. 45,46 Hi per homo sis te i ne mi nin ne den ol du ğu ok si da tif stre sin MH'nin in fil tras yo nu ve bun la rın kol lajen sen te zinin in dük si yo nu ile kar di yak hi per tro fi ye ne den ol du ğu be lir til miş tir. 46,47 Singh 42 ve ark., hi per ho mo sis te i ne mi nin neden ol du ğu kar di yak hi per tro fi yi en gel le mek için "so dyum kro moglikat (24 mg/kg/gün) ve ke to ti fen (1 mg/kg/gün) gi bi MH sta bi la tör le ri ni rat lar da kullan mış lar dır.…”

“…45,46 Hi per homo sis te i ne mi nin ne den ol du ğu ok si da tif stre sin MH'nin in fil tras yo nu ve bun la rın kol lajen sen te zinin in dük si yo nu ile kar di yak hi per tro fi ye ne den ol du ğu be lir til miş tir. 46,47 Singh 42 ve ark., hi per ho mo sis te i ne mi nin neden ol du ğu kar di yak hi per tro fi yi en gel le mek için "so dyum kro moglikat (24 mg/kg/gün) ve ke to ti fen (1 mg/kg/gün) gi bi MH sta bi la tör le ri ni rat lar da kullan mış lar dır. Ça lış ma so nun da, MH sta bi la tör le rinin kul la nıl dı ğı rat lar da an lam lı ola rak kar di yak hi per tro fi nin da ha az ol du ğu nu saptamışlardır.…”