Prdm16 Supports Arterial Flow Recovery by Maintaining Endothelial Function

Rationale: Understanding the mechanisms that regulate arterial flow recovery is important to design treatment options for peripheral artery disease patients ineligible invasive revascularization. Transcriptional orchestrators of this process represent an appealing target design. We previously identified Prdm (positive regulatory domain-containing protein) 16 as arterial-specific endothelial transcription factor but its in vivo role arteries remains completely unknown. Objective: To unravel Prdm16 under physiological and pathological conditions, more specifically during disease. Methods Results: Within vasculature, expression was strictly confined smooth muscle cells. Heterozygous loss caused a modest reduction inner diameter cell coating without compromising vasomotor function. Upon femoral ligation, +/? mice featured significantly impaired ischemic limbs. This impairment recapitulated with deletion cells ( EC-Prdm16 ?/? ) not Structural collateral remodeling normal both mice, significant dysfunction postligation present evidenced by endothelial-dependent relaxation. deficiency altered genes encoding function regulators, many related nitric oxide bioavailability Ca 2+ homeostasis. Accordingly, overexpression cultured affected total cellular levels store-operated entry. Conclusions: showed indispensable challenge because it affects structural due maintaining It, therefore, represents designing novel therapeutic strategies no-option