Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Low-Dose Fluvastatin Prevents the Functional Alterations of Endothelium Induced by Short-Term Cholesterol Feeding in Rabbit Carotid Artery

Read this article at

ScienceOpenPublisherPMC
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, are the medical treatment of choice for hypercholesterolemia. In addition to lowering serum-cholesterol levels, statins appear to promote pleiotropic effects that are independent of changes in serum cholesterol. In this study, we investigated the effects of low-dose fluvastatin on antioxidant enzyme activities (superoxide dismutase, SOD; catalase), total nitrite/nitrate levels, and vascular reactivity in 2% cholesterol-fed rabbits. This diet did not generate any fatty streak lesions on carotid artery wall. However, SOD activity significantly increased with cholesterol feeding whereas the catalase activities decreased. The levels of nitrite/nitrate, stable products of NO degradation, diminished. Moreover, dietary cholesterol reduced vascular responses to acetylcholine, but contractions to serotonin were augmented. Fluvastatin treatment abrogated the cholesterol-induced increase in SOD, increased the levels of nitric oxide metabolites in tissue, and restored both the impaired vascular responses to acetylcholine and the augmented contractile responses to serotonin without affecting plasma-cholesterol levels. Phenylephrine contractions and nitroglycerine vasodilatations did not change in all groups. This study indicated that fluvastatin treatment performed early enough to improve impaired vascular responses may delay cardiovascular complications associated with several cardiovascular diseases.

      Related collections

      Most cited references 50

      • Record: found
      • Abstract: not found
      • Article: not found

      Protein measurement with the Folin phenol reagent.

        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Endothelial nitric oxide synthase in vascular disease: from marvel to menace.

        Nitric oxide (NO*) is an important protective molecule in the vasculature, and endothelial NO* synthase (eNOS) is responsible for most of the vascular NO* produced. A functional eNOS oxidizes its substrate L-arginine to L-citrulline and NO*. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate L-arginine, and the essential cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases represent major sources of this reactive oxygen species and have been found upregulated and activated in animal models of hypertension, diabetes, and sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide (O2*-) reacts avidly with vascular NO* to form peroxynitrite (ONOO-). The cofactor BH4 is highly sensitive to oxidation by ONOO-. Diminished levels of BH4 promote O2*- production by eNOS (referred to as eNOS uncoupling). This transformation of eNOS from a protective enzyme to a contributor to oxidative stress has been observed in several in vitro models, in animal models of cardiovascular diseases, and in patients with cardiovascular risk factors. In many cases, supplementation with BH4 has been shown to correct eNOS dysfunction in animal models and patients. In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH4 levels as well.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.

          Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelial cells. Accordingly, simvastatin enhanced phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibited apoptosis and accelerated vascular structure formation in vitro in an Akt-dependent manner. Similar to vascular endothelial growth factor (VEGF) treatment, both simvastatin administration and enhanced Akt signaling in the endothelium promoted angiogenesis in ischemic limbs of normocholesterolemic rabbits. Therefore, activation of Akt represents a mechanism that can account for some of the beneficial side effects of statins, including the promotion of new blood vessel growth.
            Bookmark

            Author and article information

            Affiliations
            1Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, 35100 Izmir, Turkey
            2Department of Biochemistry, Faculty of Medicine, Ege University, 35100 Izmir, Turkey
            Author notes

            Academic Editors: J. Sastre and E. Skalidis

            Journal
            ScientificWorldJournal
            ScientificWorldJournal
            TSWJ
            The Scientific World Journal
            The Scientific World Journal
            1537-744X
            2012
            1 April 2012
            : 2012
            3324041
            22547992
            10.1100/2012/671728
            Copyright © 2012 Gulnur Sevin et al.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Research Article

            Uncategorized

            Comments

            Comment on this article