Impaired Angiogenesis and Peripheral Muscle Microcirculation Loss Contribute to Exercise Intolerance in Pulmonary Arterial Hypertension
2014
Rationale: Pulmonary arterial hypertension (PAH) is characterized by significant exercise intolerance, which is multifactorial and involves skeletal muscle alterations. There is growing evidence that microRNAs (miRs) are involved in PAH pathogenesis.Objectives: We hypothesized that miR-126, an endothelial-specific, proangiogenic miR, is down-regulated in the peripheral muscles of patients with PAH, which would account for skeletal muscle microcirculation loss and exercise intolerance.Measurements and Main Results: Patients with PAH displayed decreases in exercise capacity (V.o2max) and microcirculation loss on quadriceps muscle biopsy (in CD31+ immunofluorescence experiments) compared to control subjects. Exercise capacity correlated with muscle capillarity (r = 0.84, P < 0.01). At the cellular level, vascular endothelial growth factor (VEGF) and VEGF receptor 2 expression were similar in both groups. Conversely, PAH was associated with a 60% decrease in miR-126 expression in a quantitative reverse transc...
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