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 arterial disease (PAD) patients ineligible for invasive revascularization. Transcriptional orchestrators of this recovery process represent an appealing target for treatment design. We previously identified positive regulatory domain-containing protein (Prdm)16 as an arterial-specific endothelial transcription factor but its in vivo role in arteries remains completely unknown. Objective: To unravel the role of Prdm16 in arteries under physiological and pathological conditions, more specifically during PAD. Methods and Results: Methods and Results: Within the vasculature, Prdm16 expression was strictly expressed by arterial endothelial and smooth muscle cells. Heterozygous loss of Prdm16 caused a modest reduction of the inner arterial diameter and smooth muscle cell coating without compromising vasomotor function. Upon femoral artery ligation, Prdm16+/- mice featured significantly impaired flow recovery to ischemic limbs. This impairment was recapitulated in mice with a Prdm16 deletion specifically in endothelial cells (EC-Prdm16-/-) but not smooth muscle cells. Structural ollateral remodeling was normal in both Prdm16+/- and

Keywords:

• Nitric oxide
• Ligation
• PRDM16
• Endothelial dysfunction
• Cell biology
• Homeostasis
• Cell
• Femoral artery
• Medicine
• Endothelial stem cell

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