Telmisartan modulates mitochondrial function in vascular smooth muscle cells

The development of atherosclerosis is associated with disturbances in mitochondrial function that impair effective adenosine triphosphate (ATP) production, increase generation of superoxide and induce subsequent apoptosis in vascular smooth muscle cells (VSMCs). As peroxisome proliferator-activated receptor gamma (PPAR gamma) has a potentially important role in the regulation of mitochondrial metabolism, we studied effects of the partial PPAR gamma agonist and angiotensin receptor blocker telmisartan, on mitochondria-related cellular responses in VSMC. In human VSMC, telmisartan increased ATP levels and activation of mitochondrial complex II, succinate dehydrogenase, reduced the release of H2O2 and attenuated H2O2-induced increases in caspase 3/7 activity, a marker of cellular apoptosis. Eprosartan, an angiotensin II receptor blocker that lacks the ability to activate PPAR gamma, had no effect on these mitochondria-related cellular responses in VSMC. Studies in PPAR gamma-deficient VSMC revealed that the effects of telmisartan on mitochondrial function were largely independent of PPAR gamma although the presence of PPAR gamma modulated effects of telmisartan on H2O2 levels. These findings demonstrate that telmisartan can have significant effects on mitochondrial metabolism in VSMC that are potentially relevant to the pathogenesis of cardiovascular disease and that involve more than just angiotensin receptor blockade and activation of PPAR gamma.