Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis

Abstract

SummaryBackgroundPeroxisome proliferator-activated Receptor-γ (PPAR-γ) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-γ and RXR-α expression in different cellular populations localized within advanced carotid atherosclerosis lesions.Material/MethodsPPAR-γ and RXR-α expression was assessed by immunohistochemistry ïn 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients’ medical history, risk factors and medication intake.ResultsIncreased incidence of low PPAR-γ expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-γ expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-α expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-α expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015).ConclusionsPPAR-γ and RXR-α expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

Reduction of the level of LXRβ mRNA and PPARγ mRNA in macrophages stimulated with a macrophage colony-stimulating factor in patients with atherosclerosis

“…These pilot data pro vide evidence that a decrease in the level of PPARγ mRNA can be associated with the development of ath erosclerosis. The sequences of primers and probes Our results are consistent with those showing a decerase in PPARγ expression in atherosclerotic plaques (Soumian et al, 2005) and in macrophages which correlates with the progression of atherosclero sis (Giaginis et al, 2011).…”

Systems Pharmacology Augments Drug Safety Surveillance

“…Complexes of peroxisome proliferator‐activated receptors (PPARs) and RXRα are thought to play antiinflammatory and antiatherogenic roles in coronary artery disease . Additionally, decreased expression of RXRα has been associated with more pronounced carotid atherosclerotic disease progression; carotid atherosclerosis has been shown to be predictive of future MI …”

Retinoid X Receptor Agonists Impair Arterial Mononuclear Cell Recruitment through Peroxisome Proliferator-Activated Receptor-γ Activation

“…TNF-a has been shown to regulate RXRa expression or its subcellular localization in liver and kidney (27,28,33). More recently, Giaginis et al (34) have described that low levels of RXRa and PPARg expression correlate with advanced carotid atherosclerosis in humans. In this study, we report that RXRa is constitutively expressed in human arterial endothelial cells, but its expression is dramatically downregulated after TNF-a exposure.…”