Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

“…In the present study, we found that melatonin upregulates Bcl‐2 expression while downregulating Bax and cleaved caspase‐3 expression, suggesting that melatonin may protect EPCs against oxidative stress‐induced apoptosis. Alizarin red staining, which is a reliable marker of calcification, showed that melatonin can reverse the calcification induced by oxidative stress. Runx‐2 and OCN expression levels were both decreased after melatonin treatment under oxidative stress conditions, which also suggests that melatonin can attenuate EPC calcification.…”

Relationship between Aortic Arch Calcification, Detected by Chest X-Ray, and Renal Resistive Index in Patients with Hypertension

“…Aortic arch calcification (AAC) is caused by the progression of endothelial damage as well as inflammation and calcification in the aortic arch resulting from high blood pressure [6, 7]. Just like RRI, AAC is an important indicator of increased blood pressure burden and increased arterial stiffness [8, 9].…”

Aortic calcification in patients with rheumatoid arthritis and ankylosing spondylitis: a cross-sectional case-control study

“…Vascular calcification is a pathological process of calcium and phosphate salts accumulation within the arterial wall. It involves mainly two forms, intimal calcification in atherosclerosis and cardiac valve calcification, and artery tunica media calcification (also known as Mönckeberg sclerosis) in aging, diabetes mellitus, and chronic kidney disease mediated calcification, with various degrees overlap of them [13,14]. Vascular medial calcification increases vascular wall hardness and reducing vascular compliance.…”

“…A cohort study revealed a doubled incidence of heart failure and an increased risk of mortality attributable to heart failure in patients with RA, with the risk of heart failure associated with RF positivity, repeatedly high ESR, severe extra-articular manifestations and corticosteroid use, and a protective effect against heart failure with methotrexate use [30]. Although data are limited, studies have confirmed that low disease activity of AS did not promote vascular calcification, and inflammatory related indicators were associated with increased mortality in patients with AS [13,14]. Taking together, all these data suggested that the clinical markers of high systemic inflammation level confer an additional risk for CVD among these patients.…”