Modulation of h(2)s metabolism by statins: a new aspect of cardiovascular pharmacology.
CONCLUSIONS
Statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors) are commonly used in the treatment of cardiovascular diseases. Statins reduce plasma low-density lipoproteins, inhibit inflammatory reaction, improve endothelial function, ameliorate oxidative stress, and reduce platelet activity. Consequently, statins markedly decrease the risk of acute cardiovascular events. H(2)S is synthesized in all layers of the vascular wall, including the endothelium, smooth muscle cells, and perivascular adipose tissue (PVAT).


BACKGROUND
Recent studies demonstrate that PVAT-derived H(2)S decreases vascular tone by activating K(ATP) and/or KCNQ potassium channels in smooth muscle cells. Lipophilic atorvastatin, but not hydrophilic pravastatin, increases net H(2)S production in PVAT by inhibiting its mitochondrial oxidation, and augments the anticontractile effect of PVAT. Inhibition of H(2)S metabolism results from atorvastatin-induced decrease in coenzyme Q, which is a cofactor of H(2)S oxidation by sulfide:quinone oxidoreductase. In contrast to H(2)S, statins do not impair mitochondrial oxidation of organic substrates.


RESULTS
Taking into account antiatherosclerotic and anti-inflammatory effect of H(2)S, the gas may mediate some of the beneficial effects of statins on the cardiovascular system. In addition, specific statins differ in their ability to enhance H(2)S signaling.


CONCLUSIONS
Since both statins and H(2)S reduce ischemia-reperfusion injury, the possible effect of statins on H(2)S oxidation in other tissues such as the heart and the kidney needs to be examined. Inhibition of H(2)S metabolism may be a new therapeutic strategy to improve H(2)S signaling, especially in the mitochondrial compartment.
Department of Pathophysiology, Medical University, Lublin, Poland. jerzy.beltowski@umlub.pl
Jerzy
J
Bełtowski
Anna
A
Jamroz-Wiśniewska
D000818:Animals; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006862:Hydrogen Sulfide