Defective expression of the peroxisome regulators PPARα receptors and lysogenesis with increased cellular senescence in the venous wall of chronic venous disorder

慢性静脉疾病的静脉壁中过氧化物酶体调节剂 PPARα 受体表达缺陷和溶菌作用增强,导致细胞衰老

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作者:Miguel A Ortega #, Oscar Fraile-Martínez #, Leonel Pekarek #, Miguel A Alvarez-Mon, Ángel Asúnsolo, Lara Sanchez-Trujillo, Santiago Coca, Julia Buján, Melchor Álvarez-Mon, Natalio García-Honduvilla #, Felipe Sainz #

Abstract

The pathogenesis of chronic venous disorder (CVeD) remains partially understood. A marked wall remodeling has been shown with potential accelerated tissue senescence. We have investigated the expression of peroxisome proliferator-activated receptor (PPAR) isoforms transcription factor EB (TFEB) as regulatory molecules of cellular homeostasis and makers of peroxisomal and lysosomal biogenesis. We have also quantified p16 expression as a cellular senescence marker. In specimens of maior safena vein from 35 CVeD and 27 healthy venous controls (HV), we studied the expression of PPAR-α, PPAR-β/δ, PPAR-γ, TFEB and p16 by RT-qPCR and immunohistochemical techniques. We have demonstrated a reduced gene and protein expression of the PPAR-α and PPAR-β/δ isoform as well as that of TFEB in the venous wall of CVeD patients, suggesting an altered peroxisomal and lysosomal biogenesis associated with an increased cellular senescence shown by increased p16 expression.

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