Blood vessels sense dermal stiffness via a novel mechanotransducer, APJ

Abstract

Microvascular dysfunction accompanied by a dramatic alteration of stable capillary structure is a major hallmark of numerous age-related diseases. In skin, although the role of angiogenesis during dermal reconstitution is well documented, the functional relevance of the extracellular matrix (ECM) stiffness to vascular remodeling and its molecular mechanisms was poorly understood. Here, we developed an ex vivo 3-dimensional angiogenic model using human fat, revealing that "appropriate" stiffness induces vascular maturation associated with upregulated APJ expression, whereas the overexpression of APJ promotes the formation of large vessels even in the absence of the "appropriate" stiffness. Taken together, APJ could be a novel mechanotransducer that accelerates the maturation of cutaneous blood vessels, leading to the prevention of human skin aging.

Insight into the research frontier of hypoxia in skin health and diseases: a bibliometric analysis (Preprint)

“…Cutaneous angiogenesis is crucial for skin physiopathological functions like re-epithelialization, granulation tissue formation, extracellular matrix (ECM) synthesis and remodeling, blood flow, inflammation, the hair follicle cycle, wound healing, and cancer [78][79][80][81][82]. Vessel formation is an intricate yet coordinated process involving numerous growth factors and signaling pathways, influenced by the balance between angiogenic and antiangiogenic factors.…”