Cardiovascular disease remains the leading cause of death in the United States and vascular calcification and diabetes are both independent risk factors for incident cardiovascular disease. Fetuin-A is a hepatic secretory protein found in high concentrations in human serum and our preliminary studies suggest that feutin- A may simultaneously inhibit vascular calcification and promote insulin resistance and diabetes. We propose to explore the relationship of fetuin-A with the longitudinal development and progression of vascular calcification and diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The research evaluates biological mechanisms interlinked by a single protein and will provide new insights to cardiovascular biology and diabetology simultaneously. Conducting this research within MESA has a number of advantages. MESA stored sera from the baseline visit, allowing fetuin-A measurement. MESA extensively measured subclinical cardiovascular disease;therefore, all participants already have measurements of vascular calcification, vascular function, and metabolic parameters. Additionally, MESA participants were followed longitudinally, allowing for evaluation of the associations of baseline fetuin-A concentrations with incident vascular calcification and diabetes. We propose to take advantage of this rich resource to explore the following primary aims: (1) To determine the cross-sectional and longitudinal associations of fetuin-A with vascular calcification and vascular function;and (2) To determine the associations of serum fetuin-A concentrations with adiposity, impaired fasting glucose, and diabetes mellitus. This research will take advantage of the hypothesized countervailing effects of fetuin-A on vascular calcification and diabetes to provide new insights to cardiovascular disease pathogenesis.

Public Health Relevance

While cardiovascular disease and diabetes represent common and morbid diseases, our understanding of their pathogenesis remains incomplete. The results of this epidemiologic study will provide novel insights into their pathogenesis and may ultimately identify novel therapeutic targets for their prevention or treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL091217-01A2
Application #
7660012
Study Section
Special Emphasis Panel (ZRG1-HOP-T (03))
Program Officer
Olson, Jean
Project Start
2009-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$250,407
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Jensen, Majken K; Aroner, Sarah A; Mukamal, Kenneth J et al. (2018) High-Density Lipoprotein Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts. Circulation 137:1364-1373
Aroner, Sarah A; Mukamal, Kenneth J; St-Jules, David E et al. (2017) Fetuin-A and Risk of Diabetes Independent of Liver Fat Content: The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 185:54-64
Jensen, Majken K; Jensen, Richard A; Mukamal, Kenneth J et al. (2017) Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium. Hum Mol Genet 26:2156-2163
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Jenny, Nancy Swords; Olson, Nels C; Allison, Matthew A et al. (2016) Biomarkers of Key Biological Pathways in CVD. Glob Heart 11:327-336.e3
Polak, Joseph F; O'Leary, Daniel H (2016) Carotid Intima-Media Thickness as Surrogate for and Predictor of CVD. Glob Heart 11:295-312.e3
Aroner, Sarah A; St-Jules, David E; Mukamal, Kenneth J et al. (2016) Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 248:224-9
Criqui, Michael H; Aboyans, Victor; Allison, Matthew A et al. (2016) Peripheral Artery Disease and Aortic Disease. Glob Heart 11:313-326
Bansal, Nisha; Katz, Ronit; de Boer, Ian H et al. (2013) Influence of estrogen therapy on calcium, phosphorus, and other regulatory hormones in postmenopausal women: the MESA study. J Clin Endocrinol Metab 98:4890-8
Jensky, Nicole E; Allison, Matthew A; Loomba, Rohit et al. (2013) Null association between abdominal muscle and calcified atherosclerosis in community-living persons without clinical cardiovascular disease: the multi-ethnic study of atherosclerosis. Metabolism 62:1562-9

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