Perspective of SGLT2i in the Treatment of Abdominal Aortic Aneurysms

Abstract

:The incidence of abdominal aortic aneurysm (AAA) in the elderly is increasing year by year with high mortality. Current treatment is mainly through surgery or endovascular intervention, which is not sufficient to reduce future risk. Therefore, we still need to find an effective conservative measure as an adjunct therapy or early intervention to prevent AAA progression. Traditional therapeutic agents, such as β-receptor blockers, calcium channel blockers, and statins, have been shown to have limited effects on the growth of AAA. Recently, sodium–glucose cotransport proteins inhibitors (SGLT2is), a new class hypoglycemic drug, have shown outstanding beneficiary effects on cardiovascular diseases by plasma volume reduction, vascular tone regulation, and various unidentified mechanisms. It has been demonstrated that SGLT2i is abundantly expressed in the aorta, and some studies also showed promising results of SGLT2i in treating animal AAA models. This article aims to summarize the recent progress of AAA studies and look forward to the application of SGLT2i in AAA treatment for early intervention or adjunct therapy after surgical repair or stent graft.

Desarrollo, técnicas y utilidad de modelos animales experimentales de aneurismas aórticos torácicos y abdominales

“…Múltiples estudios se han basado en el análisis de receptores LDL y de Ang II tipo 1, que se han visto implicados en la patogenia de la aterosclerosis 50,51 , siendo una diana terapéutica utilizada el día de hoy por medio de estatinas, betabloqueadores y calcioantagonistas, aunque estos fármacos han tenido efectos limitados en controlar la progresión de AA. Recientemente se ha utilizado en animales el inhibidor del cotransportador sodio-glucosa tipo 2, que ha mostrado beneficios en trastornos cardiovasculares y se ha comprobado que se encuentra altamente expresado en la aorta 51 .…”

Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

“…In addition, ROS contribute to the reduction in NO availability which leads to endothelium dysfunction. At the same time, there is an acceleration in adhesion molecules such as ICAM-1 (intercellular adhesion molecule 1) and interlukin-1α, which enables a progressive migration of inflammatory cells, e.g., lymphocytes and macrophages [80]. The reduced availability of NO, together with ROS' influence on proinflammatory cells, increases the level of cytokine expression, which sustains the inflammation process in the aortic wall [112].…”