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In recent years it has been established that inflammation has a pathogenic role in atherosclerosis. Experimental studies have suggested that altering transcription of proinflammatory genes can result in the inhibition of atherosclerotic disease progression. Peroxisome proliferator activated receptor γ (PPARγ), a member of the nuclear receptor superfamily of ligand activated transcription factors, is highly expressed in several organs as well as in atherosclerotic plaques. Agonists of this receptor, such as rosiglitazone, pioglitazone, and troglitazone, have insulin sensitising actions and the former two agents are used clinically to treat type II diabetes. PPARγ agonists can also inhibit the transcription of proinflammatory genes within plaques and have antithrombotic effects. Furthermore, PPARγ agonists have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation, which underlies restenosis after percutaneous coronary intervention. This article summarises our current understanding of the role of PPARγ agonists in atherogenesis and discusses their potential role in the treatment of coronary artery disease and its complications.
Inflammation and coronary atherosclerosis
It is well established that an inflammatory process and specific immunological mechanisms underlie atherosclerotic plaque formation and fibrous cap disruption.1 It may therefore be speculated that antagonising key proinflammatory processes may result in delay or inhibition of disease progression.
One of the earliest physiological changes in atherosclerotic disease is reduced production of nitric oxide by the vascular endothelium (that is, endothelial dysfunction) in response to pharmacological or haemodynamic stimuli.2 Nitric oxide has several protective roles including reduction of vascular tone, inhibition of platelet aggregation, and reduction of VSMC proliferation. The earliest pathological change in atherosclerosis is the accumulation of plasma low density lipoprotein in the subendothelial space and its oxidation.3 It is still unclear whether endothelial dysfunction is a cause or a consequence of subendothelial lipid accumulation. Oxidised low density lipoprotein activates endothelial cells, which in turn synthesise surface bound …