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Conti, Marc, Isabelle M. Renaud, Bruno Poirier, Odile Michel, Marie-France Belair, Chantal Mandet, Patrick Bruneval, Isaac Myara, and Jacques Chevalier. High levels of myocardial antioxidant defense in aging nondiabetic normotensive Zucker obese rats. Am J Physiol Regul Integr Comp Physiol 286: R793-R800, 2004. First published December 11, 2003; 10.1152/ajpregu.00521.2002.--Chronic renal failure often induces left ventricular hypertrophy. We assessed whether the heart is affected in the Zucker obese rat, a model of chronic renal failure associated with obesity, glucose intolerance, and insulin resistance without hypertension or hyperglycemia. After systemic blood pressure measurement, the heart, the aorta, and the kidneys were removed from anesthetized 9- and 13-mo-old Zucker obese and lean control male rats (n = 33, n = 24, n = 25, and n = 21, respectively). Determination of left ventricular geometry, quantification of myocardium collagen density, and measurement of heart antioxidant enzyme activity were made, as well as aorta and kidney parameters. Mean blood pressure remained at a normal range whatever the age and group considered. Whereas kidney structure and function were severely impaired, no sign of myocardial infarction or inflammatory process was noticed. A moderate left ventricular hypertrophy was observed in 13-mo-old obese rats. While heart malondialdehyde was stable with age and among groups, antioxidant enzyme activity was higher in obese rats. In conclusion, in the absence of hypertensive or hyperglycemic disorders, the heart seems to display a sufficient line of defense against oxidative stress during the development of cardiac hypertrophy. left ventricular hypertrophy; renal failure; oxidative stress; Zucker rats; hyperlipidemia

Obese Zucker rat model helps examine the long-term effect of hyperinsulinemia on the migration and proliferation of aortic smooth muscle cell (SMC) induced by arterial injury with a balloon catheter. Long-lasting hyperinsulinemia induces SMC proliferation after diendothelialization, leading to higher aortic thickening in obese rats than that in lean rats. Biochemical techniques facilitate the quantitative determination of SMC proliferation within the intima-media and histological morphometric measurements help differentiate the modifications in intimal and medial cross-sectional areas and also in the number of nuclei.

Background: Viscum album (VA) preparations consist of aqueous extracts of different types of lectins of VA. Mistletoe lectins have both cytotoxic and immunomodulatory properties that support their study for the development for cancer therapy. However, the mechanisms of the anti- tumoral properties in vivo of mistletoe lectins are not fully understood. Because endothelial cells (EC) play a pivotal role in tumor angiogenesis, we tested the hypothesis that VA extracts induce endothelial cell death and apoptosis., Materials and Methods: We investigated the effect of various VA preparations on both human venous endothelial cell (HUVEC) and immortalized human venous endothelial cell line (IVEC) using morphologic assessment of EC, FACScan analysis after propidium iodine and annexin V labeling, and detection of cleavage of poly(A)DP-ribose polymerase (PARP)., Results: All tested VA preparations, except Iscador P, were cytotoxic in IVEC. Apoptosis, assessed by morphologic examination, annexin V labeling, and Western blot analysis for PARP cleavage, was involved in HUVEC cell death induced by VA preparations derived from plants that grow on oak trees (VA Qu FrF)., Conclusions: Results from the present study suggest that VA extract-induced endothelial apoptosis may explain the tumor regression associated with the therapeutic use of VA preparations and support further investigations to develop novel anti-angiogenic compounds based on mistletoe compounds.