Role of Sclerostin in Cardiovascular Disease

Golledge, Jonathan, and Thanigaimani, Shivshankar (2022) Role of Sclerostin in Cardiovascular Disease. Arteriosclerosis, Thrombosis and Vascular Biology, 42. e187-e202.

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Abstract

Sclerostin is most recognized for its role in controlling bone formation but is also expressed in the heart, aorta, coronary, and peripheral arteries. This review summarizes research on sclerostin’s role in cardiovascular disease. Rodent studies have found sclerostin to be expressed at sites of arterial calcification. In contrast, aortic sclerostin was reported to be downregulated in a mouse model of abdominal aortic aneurysm, and transgenic upregulation or administration of sclerostin was found to prevent abdominal aortic aneurysm and atherosclerosis formation. Sclerostin deficiency was reported to stimulate cardiac rupture in one rodent model. In humans, 7 of 11 studies reported a significant association between high serum sclerostin and high carotid intima media thickness. Ten of 15 studies reported a significant association between high serum sclerostin and severe arterial calcification. Twelve of 14 studies reported a significant association between high serum sclerostin and high arterial stiffness or atherosclerosis severity. Four of 9 studies reported a significant association between high serum sclerostin and high risk of cardiovascular events. A meta-analysis of randomized controlled trials suggested that administration of the sclerostin blocking antibody romosozumab did not significantly increase the risk of major adverse cardiovascular events (risk ratio, 1.14 [95% CI, 0.83–1.57]; P=0.54) or cardiovascular death (risk ratio, 0.92 [95% CI, 0.53–1.59]; P=0.71). Human genetic studies reported variants predisposing to low arterial sclerostin expression were associated with a high risk of cardiovascular events. Overall, past research suggests a cardiovascular protective role of sclerostin but findings have been inconsistent, possibly due to variations in study design, the unique populations and models studied, and the heterogeneous methods used.

Item ID: 75359
Item Type: Article (Research - C1)
ISSN: 1524-4636
Keywords: abdominal aortic aneurysm, aorta, atherosclerosis, cardiovascular disease, osteoporosis, Wnt pathway
Copyright Information: © 2022 American Heart Association, Inc.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1180736
Date Deposited: 29 Jun 2022 07:36
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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