HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/2/H679    most recent 00145.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Joseph, J. Articles by Kennedy, R. H. Search for Related Content PubMed PubMed Citation Articles by Joseph, J. Articles by Kennedy, R. H.

Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats

Departments of ¹Internal Medicine, ²Pharmaceutical Sciences, ³Pathology, ⁴Pharmacology and Toxicology, and ⁵Surgery, Central Arkansas Veterans Healthcare System, and University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

Submitted 19 February 2003 ; accepted in final form 23 April 2003

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.

homocysteine; diastolic dysfunction; cardiac remodeling; collagen; cardiomyocyte

This article has been cited by other articles:

				R. R. Lamberts, E. Caldenhoven, M. Lansink, G. Witte, R. J. Vaessen, J. A. St Cyr, and G. J. M. Stienen Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1869 - H1876. [Abstract] [Full Text] [PDF]

				M. Herrmann, O. Taban-Shoma, U. Hubner, A. Pexa, H. Kilter, N. Umanskaya, R. Hans Straub, M. Bohm, and W. Herrmann Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic Peptide in Rats Clin. Chem., April 1, 2007; 53(4): 773 - 780. [Abstract] [Full Text] [PDF]

				K. Nasir, M. Tsai, B. D. Rosen, V. Fernandes, D. A. Bluemke, A. R. Folsom, and J. A.C. Lima Elevated Homocysteine Is Associated With Reduced Regional Left Ventricular Function: The Multi-Ethnic Study of Atherosclerosis Circulation, January 16, 2007; 115(2): 180 - 187. [Abstract] [Full Text] [PDF]

				M. Herrmann, S. Muller, I. Kindermann, L. Gunther, J. Konig, M. Bohm, and W. Herrmann Plasma B vitamins and their relation to the severity of chronic heart failure Am. J. Clinical Nutrition, January 1, 2007; 85(1): 117 - 123. [Abstract] [Full Text] [PDF]

				J. Joseph, R. H. Kennedy, S. Devi, J. Wang, L. Joseph, and M. Hauer-Jensen Protective role of mast cells in homocysteine-induced cardiac remodeling Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2541 - H2545. [Abstract] [Full Text] [PDF]

				M. Boerma, J. Wang, J. Wondergem, J. Joseph, X. Qiu, R. H. Kennedy, and M. Hauer-Jensen Influence of Mast Cells on Structural and Functional Manifestations of Radiation-Induced Heart Disease Cancer Res., April 15, 2005; 65(8): 3100 - 3107. [Abstract] [Full Text] [PDF]

				M. Cesari, M. Zanchetta, A. Burlina, L. Pedon, G. Maiolino, D. Sticchi, A. C. Pessina, and G. P. Rossi Hyperhomocysteinemia Is Inversely Related With Left Ventricular Ejection Fraction and Predicts Cardiovascular Mortality in High-Risk Coronary Artery Disease Hypertensives Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 115 - 121. [Abstract] [Full Text] [PDF]

				R. H. Kennedy, R. Owings, N. Shekhawat, and J. Joseph Acute negative inotropic effects of homocysteine are mediated via the endothelium Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H812 - H817. [Abstract] [Full Text] [PDF]

				E. Walker, J. Black, C. Parris, E. C. Bryda, S. Cansino, L. Hunt, J. Chappell, P. Wehner, M. Studeny, and G. L. Wright Effect of Experimental Hyperhomocysteinemia on Cardiac Structure and Function in the Rat Ann. Clin. Lab. Sci., April 1, 2004; 34(2): 175 - 180. [Abstract] [Full Text] [PDF]