Mast cells (MCs) are proinflammatory cells that play important roles in allergic responses, tumor growth, obesity, diabetes, atherosclerosis, and abdominal aortic aneurysm (AAA). Although the presence and function of MCs in atherosclerotic lesions have been thoroughly studied in human specimens, in primary cultured vascular cells, and in atherosclerosis in animals, their role in AAA was recognized only recently. Via multiple activation pathways, MCs release a spectrum of mediators including histamine, inflammatory cytokines, chemokines, growth factors, proteoglycans, and proteases to activate neighboring cells, degrade extracellular matrix proteins, process latent bioactive molecules, promote angiogenesis, recruit additional inflammatory cells, and stimulate vascular cell apoptosis. These activities associate closely with medial elastica breakdown, medial smooth-muscle cell loss and thinning, outer media and adventitia inflammation, aortic wall expansion, endothelium erosion, and eventual rupture and thrombosis. Experimental animal AAA models and MC reconstitution technique allowed examination of a direct role of MCs in AAA pathogenesis, and identification of the exact role of each MC-derived molecule. Genetic deficiency of MCs, pharmacological inhibition of MC degranulation, absence of MC-specific chymase and tryptase, or inhibition of these proteases, all effectively attenuated or abolished experimental AAA growth. The role of MCs have been reproduced in humans in several case-control studies, and two cohort studies showing the systemic level of MC specific chymase and tryptase is associated with aneurysmal growth rate, need for later aneurysmal repair and even overall mortality. These observations offer new opportunities to prevent or slow AAA growth in humans, and specific antimastcell drugs inhibiting degranulation of MCs have been used for especially allergic diseases for decades. It clearly calls for randomized clinical trials as no medical treatment to inhibit AAA progression so far have shown to be efficient.
Keywords: Abdominal aortic aneurysm, mast cell, inflammation, extracellular matrix protein, chymase, tryptase, angiogenesis, apoptosis.
Cerebral Aneurysm Formation in Nitric Oxide Synthase-3 Knockout Mice
Current Neurovascular Research IgG4 Related Syndrome: Another Multiorgan Disease in the Interest Field of Internal Medicine
Current Pharmaceutical Design Statins: The Holy Grail of Abdominal Aortic Aneurysm (AAA) Growth Attenuation? A Systematic Review of the Literature
Current Vascular Pharmacology The Coronary Collateral Circulation in Man
Current Cardiology Reviews An Evidence-Based Review of Off-Label Uses of Polidocanol
Current Clinical Pharmacology Intracranial Non-traumatic Aneurysms in Children and Adolescents
Current Pediatric Reviews A Pictorial Review of Intracranial Haemorrhage Revisited
Current Medical Imaging Abdominal Aortic Aneurysm: What About Screening?
Current Pharmaceutical Design Editorial (Thematic Issue: Novel Insights on Aortic Aneurysm)
Current Pharmaceutical Design Giant Pulmonary Artery Aneurysm Secondary To Patent Ductus Arteriosus: A Case Report
Current Cardiology Reviews Impact of Tobacco Smoking on Lipid Metabolism, Body Weight and Cardiometabolic Risk
Current Pharmaceutical Design Statins Exert Multiple Beneficial Effects on Patients Undergoing Percutaneous Revascularization Procedures
Current Drug Targets Anticoagulation in Patients with Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry Cardiovascular Involvement in Pediatric Systemic Autoimmune Diseases: The Emerging Role of Noninvasive Cardiovascular Imaging
Inflammation & Allergy - Drug Targets (Discontinued) miR-29c-3p is an Effective Biomarker of Abdominal Aortic Aneurysm in Patients Undergoing Elective Surgery
MicroRNA Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target
Current Drug Targets Drug Therapy for Abdominal Aortic Aneurysms Utilizing Omega-3 Unsaturated Fatty Acids and Their Derivatives
Current Drug Targets Homocysteine and Non-Cardiac Vascular Disease
Current Pharmaceutical Design An Update on the Role of the Quality of LDL in Cardiovascular Risk:The Contribution of the Universities of Palermo and Zurich
Recent Patents on Cardiovascular Drug Discovery (Discontinued) Nosocomial Infections and Antimicrobial Treatment in Coiled Patients with Aneurysmal Subarachnoid Hemorrhage
Current Drug Targets