ABSTRACT
Mitochondrial mechanism of oxidative stress and matrix metalloproteinase (MMP) activation was unclear. Our recent data suggested that MMPs are localized to mitochondria and activated by peroxynitrite, which causes cardiovascular remodeling and failure. Recently, we have demonstrated that elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) increase oxidative stress in the mitochondria. Although HHcy causes heart failure, interestingly, it is becoming very clear that Hcy can generate hydrogen sulfide (H2S), if the enzymes cystathionine β-synthase (CBS) and cystathionine -lyase (CGL) are present. H2S is a strong anti-oxidant and vasorelaxing agent. Paradoxically, it is interesting that Hcy, a precursor of H2S can be cardioprotective. The CGL is ubiquitous, while the CBS is not present in the vascular tissues. Therefore, under normal condition, only half of Hcy can be converted to H2S. However, there is strong potential for gene therapy of CBS to vascular tissue that can mitigate the detrimental effects of Hcy by converting it to H2S. This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy.
Subject(s)
Animals , Gene Deletion , Heart Failure/genetics , Heart Failure/metabolism , Heart Failure/physiopathology , Homocysteine/metabolism , Humans , Hydrogen Sulfide/metabolism , Myocardial Contraction , Receptors, N-Methyl-D-Aspartate/deficiency , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolismABSTRACT
Objective To study the role of total flavonoids of hippophae rhamnoides in improving contactile function of stretched cardiac myocyte.Method Flavonoids were given to stretched myocytes which were proved their contractile function decline and then myocyte contractile mechanics characteristics and calcium transfer were measured.Result Flavonoids increased myocyte contractility,as indicated by myocyte shortening,velocity of shortening,peak+dL/dt and peak-dL/dt during shortening,in a concentration-dependent manner (r>0.9,P<0.001),and with no relation to the intracellular calcium transfer in the myocytes.Conclusion Flavonoids of the traditional Chinese drug hippophae rhamnoids is effective in improving the contractile function of stretched cardiac myocyte in low dosage.