The role of Epsins in atherosclerosis: From molecular mechanisms to therapeutic applications.
Siarhei A Dabravolski, Alexey V Churov, Alessio L Ravani, Amina E Karimova, Igor G Luchinkin, Vasily N Sukhorukov, Alexander N Orekhov
Author Information
Siarhei A Dabravolski: Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel 2161002, Israel. Electronic address: sergedobrowolski@gmail.com.
Alexey V Churov: Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia; Pirogov Russian National Research Medical University, Russia Gerontology Clinical Research Centre, Moscow, Institute on Ageing Research, Russian Federation, 16 1st Leonova Street, 129226 Moscow, Russia.
Alessio L Ravani: Institute for Atherosclerosis Research, Osennyaya Street 4-1-207, 121609 Moscow, Russia.
Amina E Karimova: Faculty of Biology and Biotechnology, National Research University Higher School of Economics, 33, Profsoyuznaya Street, Building 4, 117418 Moscow, Russia.
Igor G Luchinkin: Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia.
Vasily N Sukhorukov: Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia; Institute of Human Morphology, Petrovsky Russian National Center of Surgery, 2 Abrikosovsky Lane, 119991 Moscow, Russia.
Alexander N Orekhov: Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia.
Atherosclerosis is a multifaceted disease characterised by chronic inflammation and vascular remodelling, leading to plaque formation and cardiovascular complications. Recent evidence highlights the critical role of epsins, a family of endocytic proteins, in the pathogenesis of atherosclerosis. This manuscript explores the multifarious functions of epsins in atherosclerosis, focusing on their involvement in angiogenesis, lymphangiogenesis, and the modulation of key signalling pathways. We discuss how epsins facilitate EndoMT through their interaction with the TGF�� signalling pathway, which contributes to vascular smooth muscle cell-like phenotypes and plaque instability. Additionally, we examine the therapeutic potential of targeting epsins, elucidating their interactions with crucial partners such as LDLR, LRP-1, and TLR 2/4, among others, in mediating lipid metabolism and inflammation. Furthermore, we highlight the promising prospects of epsin-targeting peptides and small interfering RNAs as therapeutic agents for atherosclerosis treatment. Despite these advancements, the research faces limitations, including a reliance on specific mouse models and a need for comprehensive studies on the long-term effects of epsin modulation. Therefore, future investigations should focus on elucidating the detailed mechanisms of epsin function and their implications in cardiovascular health, fostering collaborations to translate basic research into innovative therapeutic strategies. This work underscores the necessity for further exploration of epsins to unlock their full therapeutic potential in combating atherosclerosis and related cardiovascular diseases.
