title: [Benefit of vanadium compound in therapy for cardiovascular diseases].
abstract: There is an increase in cardiovascular disease and cardiovascular risk after menopause. Development of animal models of cardiovascular disease in postmenopause is critical to define pathophysiological mechanism underlying cardiovascular injury and to advance in the therapy. We first developed a rat model of postmenopausal cardiac myocardial hypertrophy and dysfunction. Rats were surgically ovariectomized (OVX) and subjected to pressure overload (PO) by aortic banding. We found marked reduction of protein kinase B (Akt) activity and endothelial nitric oxide synthase (eNOS) phosphorylation. Since we found bis(1-oxy-2-pyridinethiolato) oxovanadium (IV) (VO(OPT)), as strong stimulator of Akt in vivo, we treated it for OVX-PO hypertrophy model. Interestingly, VO(OPT) treatment significantly attenuated cardiac hypertrophy and prevented the progress from hypertrophy to heart failure. The cardioprotective effects of VO(OPT) were closely associated with increases in Akt activity and eNOS phosphorylation in the left ventricule. The cardiac hypertrophy and contractile dysfunction were significantly improved by VO(OPT) treatment. Taken together vanadium compound are possible therapeutics for cardiac hypertrophy and heart failure following hypertension in postmenopausal women.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. kfukunaga@m.tohoku.ac.jp
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology; D002316:Cardiotonic Agents; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006352:Heart Ventricles / Q000201:enzymology; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D017698:Postmenopause / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012306:Risk; D017968:Vanadium Compounds / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D017968:Vanadium Compounds; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt