Expression of Peroxisome Proliferator-Activated Receptor- in Vascular Smooth Muscle Cells Is Upregulated in Cystic Medial Degeneration of Annuloaortic Ectasia in Marfan Syndrome

Background—Cystic medial degeneration (CMD) is a histological abnormality that is common in annuloaortic ectasia (AAE) and aortic dissection with Marfan syndrome. Apoptosis and loss of vascular smooth muscle cells (VSMCs) is one of the features of CMD, but little is known about its pathogenesis. Peroxisome proliferator-activated receptor(PPAR ), a transcription factor of the nuclear receptor superfamily, has been reported to show antiproliferative effects on VSMCs as well as anti-inflammatory effects on macrophages. PPAR agonist has been recently reported to induce apoptosis of cultured VSMCs. Methods—We examined the histopathology of ascending aortas in AAE of Marfan patients (n 21) and control patients (n 6) at surgery. RT-PCR was performed to demonstrate expression of PPAR in CMD. Localization of PPAR was determined by double immunostaining using antibodies against PPAR and cell-specific markers (ie, SMCs, macrophages, and T lymphocytes). Results—PPAR expression was upregulated in AAE samples but minimal in control samples by RT-PCR (P 0.07). Immunoreactivity against PPAR in numerous nuclei of VSMCs was observed in CMD lesions. Severity of CMD correlated with positive immunoreactivity of PPAR in medial VSMCs (P 0.03). No inflammatory cells (ie, macrophages or T lymphocytes) were detected in CMD lesions. Conclusion—PPAR expression is upregulated in SMCs of CMD without any inflammatory response. Activated PPAR in VSMCs might be involved in the pathogenesis of CMD in Marfan’s aortas. Regulation of PPAR might lead to clinical implication in protection against progression of AAE. (Circulation. 2002;106[suppl I]:I-259-I-263.)