Characterizing Aortic Smooth Muscle Cell Phenotype in the Setting of Thoracic Aortic Aneurysm

INTRODUCTION Bicuspid aortic valve disease (BAV) is the most common congenital cardiac malformation occurring in 1-2% of the general population [1] [2]. Normally, the aortic valve is separated into 3 valves. However, BAV involves fusing of the valvular leaflets during development, resulting in a 2-valve structure instead of the normal 3-valve structure. BAV predisposes patients to a thoracic aortic aneurysm, which is characterized by an enlargement of the ascending aortic vessel [3]. Causes of aneurysm can be attributed to an underlying weakness in the vessel walls. These aneurysms can be life threatening, particularly if they result in a ruptured vessel wall. It has been shown that patients with BAV disease typically present a thoracic aortic aneurysm up to 10-15 years earlier than patients with a normal tricuspid aortic valve (TAV) [3]. Prior to a thoracic aortic aneurysm, degeneration at the tissue level is prevalent. Degeneration can cause weakening of the aortic wall, which then can lead to aneurysm. While it is known that patients with BAV have increased risk of a thoracic aortic aneurysm, the cellular mechanisms remain unknown. Understanding the cellular mechanisms is important in studying pathological characteristics of the aorta, such as BAV [4]. Smooth muscle cells play a key role in tissue damage repair and could help to explain the degeneration of tissue prior to thoracic aortic aneurysms. The smooth muscle cells have remarkable plasticity and can exist in a synthetic phenotype, where the cells are continually growing and proliferating, or in a contractile phenotype, where the cells contribute to regulation of vessel tone [4]. Smooth muscle cells alter their phenotype based on environmental cues such as nutrients availability [5]. Fetal bovine serum is used as a growth factor when culturing cells in vitro that offers the cells enough nutrients to continually proliferate. Depending on the smooth muscle cells’ phenotype, the cells can express different proteins suited for that phenotype’s particular function. Proteins that are characteristic of the contractile phenotype include smooth muscle actin, calponin, and smoothelin [5]. Studying the cellular differences, specifically in smooth muscle cells, between patients with bicuspid and tricuspid aortic valves may indicate why the pathology of a bicuspid aortic valve can initiate thoracic aortic aneurysms earlier in these patients. Therefore, a look at the phenotype of the smooth muscle cells in the aorta when they are subject to different environmental cues, such as nutrient levels, is important.