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(Hypertension. 2001;37:760.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Workshop: Excess Growth and Apoptosis

Is Hypertension a Case of Accelerated Aging of Cardiovascular Cells?

Pavel Hamet; Nathalie Thorin-Trescases; Pierre Moreau; Pierre Dumas; Ben-Sung Tea; Denis deBlois; Vladimir Kren; Michal Pravenec; Jaroslav Kunes; Yulin Sun; Johanne Tremblay

From Centre de recherche, Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada (P.H., N.T.-T., P.M., P.D., B.-S.T., D.d.B., Y.S., J.T.); Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic (M.P.); and Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic (V.K., M.P., J.K.).

Correspondence to Pavel Hamet, Laboratory of Molecular Medicine, Centre de recherche, CHUM-Hôtel-Dieu, 3850 St Urbain St, Montréal, Québec H2W 1T8, Canada. E-mail hamet{at}ere.umontreal.ca

Several groups including ours have demonstrated cardiac hyperplasia in neonates from genetically hypertensive rat strains. We have shown that similar problems exist in the kidney as well. More recently, we found that excessive heart and kidney weight is neonatally related to inhibition of apoptosis. Using recombinant inbred strains derived from a reciprocal cross between Brown Norway and spontaneously hypertensive rat progenitor strains, we mapped the inhibition of neonatal apoptosis to 2 distinct loci on chromosomes 1 (Myl 2) and 18 (Abrb 2). Positional candidate genes at these loci are being explored. These studies have also demonstrated that the loci determining kidney and heart weights in neonates are distinct from those determining increased organ weight in adults. The impact of blood pressure per se is also divergent because adult kidney weight is negatively correlated whereas heart weight is positively correlated with it. Analyses by extremes of low and high percentiles from fetal life to adulthood identified a single locus determining heart weight at Acaa on chromosome 8 in newborn (P=0.0003) and adult (P=0.016) rats. The Acaa region contains a DNA mismatch repair gene (hMLH1). The kinetics of neonatal growth through adulthood by prelabeling DNA with [³H]thymidine in pregnant mares showed that although the growth process is complex and nonlinear in the kidney of hypertensive rats, there is an increased turnover of cells, that is, reduced half-life of DNA. This observation is supported by the presence of shorter telomere fragments in kidneys of spontaneously hypertensive rats. These studies suggest that cardiovascular cells from hypertensive animals are subject to accelerated turnover, potentially leading to their accelerated aging.

Key Words: hypertension • genetics • telomeres • growth • apoptosis • aging

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