Nassar Alice, Wagura Elizabeth, Loukas Marios
Department of Anatomical Sciences, St. George's University, School of Medicine, West Indies, Grenada; Department of Internal Medicine, Trinity Health Hospital, Livonia, Michigan, USA.
Department of Anatomical Sciences, St. George's University, School of Medicine, West Indies, Grenada.
Cardiovasc Pathol. 2025 Mar-Apr;75:107716. doi: 10.1016/j.carpath.2025.107716. Epub 2025 Jan 6.
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.
血管闭塞性疾病仍然是全球主要的健康负担，因此有必要更深入地了解减轻其影响的适应性反应。动脉生成是指侧支血管在动脉闭塞时的生长和重塑，是一种重要的防御机制，可抵消流体剪切应力诱导的血管狭窄或闭塞。虽然驱动动脉生成的物理因素已得到广泛研究，但其中涉及的具体细胞介质却知之甚少。值得注意的是，先天免疫细胞和适应性免疫细胞，尤其是肥大细胞，在动脉生成中的作用受到的关注有限。本系统综述通过研究肥大细胞对动脉生成中血管细胞增殖和白细胞募集的贡献，填补了这一知识空白。使用系统评价和荟萃分析的首选报告项目对主要数据库进行全面检索，揭示了肥大细胞、炎症细胞、先天免疫细胞和生长因子在动脉生成中的关键联系。我们的研究结果突出了肥大细胞激活、切应力作用和促动脉生成生长因子募集的分子机制。此外，我们探讨了包括亚硝酸盐、双嘧达莫、凝血酶和眼镜蛇毒液在内的内源性和外源性因素，这些因素触发肥大细胞介导的促动脉生成因子释放。此外，我们研究了重组甲状旁腺激素（rPTH）治疗对骨缺损和同种异体移植愈合中肥大细胞数量和动脉生成的影响。我们的综述为肥大细胞的促动脉生成作用提供了有力证据，尤其是在血管闭塞的早期炎症阶段，这表明靶向肥大细胞激活可能是增强动脉生成和治疗缺血相关疾病的一种有前景的治疗策略。
