Novel pharmacological approaches in abdominal aortic aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a progressive dilation of the abdominal aorta, boosted by atherosclerosis, ageing, and smoking as major risk factors. Aneurysm growth increases the risk of aortic rupture, a life-threatening emergency with high mortality rates. Despite the increasing progress in our knowledge about the etiopathology of AAA, an effective pharmacological treatment against this disorder remains elusive and surgical repair is still the unique available therapeutic approach for high-risk patients. Meanwhile, there is no medical alternative for patients with small aneurysms but close surveillance. Clinical trials assessing the efficacy of antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate a clear benefit limiting AAA growth, while data from ongoing clinical trials addressing the benefit of metformin on aneurysm progression are eagerly awaited. Recent preclinical studies have postulated new therapeutic targets and pharmacological strategies paving the way for the implementation of future clinical studies exploring these novel therapeutic strategies. This review summarises some of the most relevant clinical and preclinical studies in search of new therapeutic approaches for AAA.

Colchicine protects against the development of experimental abdominal aortic aneurysm

“…, and AAA is positively related to vascular inflammatory infiltration. Nowadays, no proven pharmacological treatment is available to limit AAA formation and progression [ 51 ]. Maybe colchicine could not limit the growth of AAA eventually, our work indicated that colchicine played a protective role at the early stage of AAA formation, and further studies are needed.…”

PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets

“…The clinical management of patients with AAA is limited to surgical intervention of large aneurysms, a high-risk surgery with high healthcare costs. Unfortunately, no pharmacological strategies are currently available to limit disease progression and reduce the risk of aneurysm rupture; therefore, a deeper understanding of the pathophysiology of these diseases is essential to identify new therapeutic targets that improve patient care [62].…”

Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical

“…Risk factors for AAA in diagnostic screening include hypertension, atherosclerosis, diabetes, etc, medications targeting these risk factors related diseases may help slow the progression of AAA, reducing the risk of rupture. In light of these information, the results of preclinical studies in animal models suggest that statins, antihypertensive drugs, doxycycline, metformin, and others have delaying effect on AAA progression ( 8 – 10 ). However, the three main AAA models currently available are elastase, CaCl2, and angiotensin II (AngII)/apolipoprotein E (AapoE)-deficient mouse models, each of which has defects that may not translate the findings to human AAA, and there is currently insufficient evidence from multiple clinical drug trials to conclusively prove the complete efficacy of these drugs in treatment ( 11 , 12 ).…”