Mast cells and arteriogenesis: A systematic review

Vascular occlusive diseases remain a major health burden worldwide, necessitating a deeper understanding of the adaptive responses that mitigate their impact. Arteriogenesis, the growth and remodeling of collateral vessels in response to arterial occlusion, is a vital defense mechanism that counteracts fluid shear stress-induced vascular stenosis or occlusion. While physical factors driving arteriogenesis have been extensively studied, the specific cellular mediators involved are poorly understood. Notably, the role of innate and adaptive immune cells, particularly mast cells, in arteriogenesis has received limited attention. This systematic review bridges this knowledge gap by investigating the contribution of mast cells to vascular cell proliferation and leukocyte recruitment in arteriogenesis. A comprehensive search of major databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines reveals the critical connection between mast cells, inflammatory cells, innate immune cells, and growth factors in arteriogenesis. Our findings highlight the molecular mechanisms of mast cell activation, sheer stress exertion, and pro-arteriogenic growth factor recruitment. Furthermore, we explore the endogenous and exogenous factors, including nitrite, dipyridamole, thrombin, and cobra venom, triggering mast cell-mediated release of pro-arteriogenic factors. Additionally, we examine the impact of recombinant parathyroid hormone (rPTH) therapy on mast cell numbers and arteriogenesis in bone defect and allograft healing. Our review provides compelling evidence for the pro-arteriogenic role of mast cells, particularly during the early inflammatory phase of vessel occlusion, suggesting that targeting mast cell activation may be a promising therapeutic strategy for enhancing arteriogenesis and treating ischemia-related diseases.