Partial Peroxisome Proliferator-Activated Receptor Agonist Angiotensin Receptor Blockers

Abstract

Background and Purpose: Although their primary mechanism of action is blood pressure lowering, emerging data suggest that select angiotensin receptor blockers (ARBs), which partially activate the peroxisome proliferator-activated receptor γ (PPAR-γ), may effectively treat insulin resistance and dyslipidemia without the toxicity sometimes associated with full PPAR-γ agonists. Since up to 50% of the patients with ischemic stroke and transient ischemic attack harbor insulin resistance, drugs that simultaneously control hypertension and insulin resistance could be particularly useful for stroke prevention. Summary of Review: This review presents the experimental and preliminary clinical evidence supporting a promising role for partial PPAR-γ agonist ARBs in treating insulin resistance and the metabolic syndrome in patients with ischemic cerebrovascular disease. Conclusion: Partial PPAR-γ agonist ARBs by virtue of their multiple beneficial mechanisms of action could provide a single multipronged strategy for reducing future vascular events in persons with, or at risk for, stroke.

Peroxisome Proliferator‐Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

“…In this regard, several lines of clinical evidence support the use of two Angiotensin receptor blockers (ARBs), telmisartan and irbesartan, in treating hyperlipidemia and insulin resistance [24]. In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), subjects with increased risk for cardiovascular events were randomized to receive telmisartan, ramipril, or a combination of telmisartan and ramipril, while in the companion Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND) trial, subjects intolerant to ACE inhibitors were randomized to telmisartan or placebo [25].…”

Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?

“…PPAR heterodimerizes with retinoid X receptor (RXR) and the ligand-activated PPAR binds to a specific DNA binding site, termed the PPAR response element (PPRE) [3, 4] to become transcriptionally active. There are three PPAR subtypes—PPAR α , PPAR δ (also known as PPAR β ), and PPAR γ , which regulate gene expression in a variety of process, including lipid and glucose metabolism, atherosclerotic plaque formation, cellular differentiation, angiogenesis, inflammation, hypertension, and heart failure [5–7]. Although three subtypes of PPAR share many aspects of biology, each of the isoforms has specific tissue distribution, ligand selectivity, and unique biological effects [8].…”

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

“…The fact that the cardioprotective properties of fibrates may be largely independent of their effects on plasma lipid levels, especially in subjects with features of the metabolic syndrome [140], suggests that the increase in adiponectin may contribute to the protective effect of fibrates against CVD. Recently, some sort of ARBs such as telmisartan and to a lesser extent irbesartan partially activate PPAR- γ and effectively treat insulin resistance and dyslipidemia without the toxicity sometimes associated with full PPAR- γ agonists [141, 142]. Statins can also enhance PPAR- γ activation, which may at least in part be involved in their antioxidant or anti-inflammatory potential [139].…”