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      Attenuated Progression of Coronary Artery Disease After 6 Years of Multifactorial Risk Intervention : Role of Physical Exercise

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          Abstract

          It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years. Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03+/-1.03 versus 5.67+/-1.01 mmol/L; P<.03) and triglyceride levels (1.94+/-0.8 versus 1.6+/-0.89 mmol/L; P<.005) and maintained their initial body mass index (26+/-2 versus 27+/-2 kg/m2; P=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05+/-1.02 versus 5.79+/-0.88 mmol/L; triglycerides, 2.25+/-1.28 versus 1.85+/-0.96 mmol/L [both P=NS]; body mass index, 26+/-2 versus 28+/-3 kg/m2 [P<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166+/-59 versus 212+/-89 W; P<.001), whereas values remained essentially unchanged in the control group (165+/-51 versus 170+/-60 W; P=NS; between groups, P<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (P<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784+/-384 kcal/wk (approximately 4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes. After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.

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          Most cited references16

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          Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.

          Endothelium-derived relaxing factor has been recently identified as nitric oxide. The purpose of this study was to determine if vasodilator drugs that generate nitric oxide inhibit vascular smooth muscle mitogenesis and proliferation in culture. Three chemically dissimilar vasodilators, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, dose-dependently inhibited serum-induced thymidine incorporation by rat aortic smooth muscle cells. Moreover, 8-bromo-cGMP mimicked the antimitogenic effect of the nitric oxide-generating drugs. The antimitogenic effect of S-nitroso-N-acetylpenicillamine was inhibited by hemoglobin and potentiated by superoxide dismutase, supporting the view that nitric oxide was the ultimate effector. Sodium nitroprusside and S-nitroso-N-acetylpenicillamine significantly decreased the proliferation of vascular smooth muscle cells. Moreover, the inhibition of mitogenesis and proliferation was shown to be independent of cell damage, as documented by several criteria of cell viability. These results suggest that endogenous nitric oxide may function as a modulator of vascular smooth muscle cell mitogenesis and proliferation, by a cGMP-mediated mechanism.
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            Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells.

            Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. Regulation of VCAM-1 gene expression may be coupled to oxidative stress through specific reduction-oxidation (redox) sensitive transcriptional or posttranscriptional regulatory factors. In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC). Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC). PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion. In a distinct pattern, PDTC partially inhibited E-selectin gene expression in response to TNF alpha but not to LPS, IL-1 beta, or PIC. TNF alpha and LPS-mediated transcriptional activation of the human VCAM-1 promoter through NF-kappa B-like DNA enhancer elements and associated NF-kappa B-like DNA binding proteins was inhibited by PDTC. These studies suggest a molecular linkage between an antioxidant sensitive transcriptional regulatory mechanism and VCAM-1 gene expression that expands on the notion of oxidative stress as an important regulatory signal in the pathogenesis of atherosclerosis.
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              Cardiac Rehabilitation After Myocardial Infarction

                Author and article information

                Journal
                Circulation
                Circulation
                Ovid Technologies (Wolters Kluwer Health)
                0009-7322
                1524-4539
                October 21 1997
                October 21 1997
                : 96
                : 8
                : 2534-2541
                Affiliations
                [1 ]From Medizinische Universitätsklinik Heidelberg, Abteilung Innere Medizin III–Kardiologie (J.N., T.V., K.H., C.M., B.K., C.W., G. Schlierf, R.Z., W.K.), Heidelberg, Germany; Herzzentrum der Universität Leipzig (R.H., G. Schuler), Abteilung Innere Medizin–Kardiologie, Leipzig, Germany; and Herzzentrum Lahr (E. von H.), Abteilung Kardiologie, Lahr, Germany.
                Article
                10.1161/01.CIR.96.8.2534
                9355890
                83433a6d-8d96-472c-8c22-b165fd07030f
                © 1997
                History

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