Proteomic Markers for Vascular Disease

The Atherosclerosis and Lipid Genomics Laboratory has a long-standing interest in circulating biomarkers of cardiovascular disease.

For example, in the Proteomic Markers of Arteriosclerosis Study, our research team investigated how novel protein markers in etiologic pathways of vascular disease relate to quantitative phenotypes (coronary artery calcium, cerebral leukoaraiosis, albuminuria and ankle-brachial index) of arteriosclerotic vascular disease. This study was conducted in participants of the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

Recent studies in Dr. Kullo's laboratory include biomarker research to predict adverse outcomes in patients with stable coronary heart disease (CHD).

Supported by the National Heart, Lung, and Blood Institute, the Atherosclerosis and Lipid Genomics Lab obtained samples from the Prevention of Events with Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) clinical trial. These samples were used to measure osteopontin (OPN), a protein responsible for the maintenance of endothelial cell integrity, inflammatory response and vascular calcification.

The goal was to investigate if OPN is associated with cardiovascular death, fatal and nonfatal myocardial infarction, ischemic stroke, and heart failure.

Related publications

• Ye Z, Ali Z, Klee GG, Mosley Jr TH, Kullo IJ. Associations of candidate biomarkers of vascular disease with the ankle-brachial index and peripheral arterial disease. Am J Hypertens. 2013;26(4):495-502. [PMID: 23467205; PMC3626040].
• Coutinho T, Mosley T, Kullo IJ. Biomarkers associated with pulse pressure in African-Americans and non-Hispanic whites. Am J Hypertens. 2012;25(2):145-51. [PMID:22012208; PMC3707798].
• Roberts RO, Geda YE, Knopman DS, Boeve BF, Christianson TJ, Pankratz VS, Kullo IJ, Tangalos EG, Ivnik RJ, Petersen RC. Association of C-reactive protein with mild cognitive impairment. Alzheimers Dement 2009;5(5):398-405. [PMID: 19751919; PMC2851170].
• Khawaja FJ, Kullo IJ. Novel markers of peripheral arterial disease. Vasc Med 2009;14(4):381-92. [PMID: 19808725; PMC2901866].
• Fulop T, Rule AD, Schmidt DW, Wiste HJ, Bailey KR, Kullo IJ, et al. C-reactive protein among community-dwelling hypertensives on single-agent antihypertensive treatment. J Am Soc Hypert 2009;3(4):260-6. [PMID: 20161163; PMC2739300].
• Kim CX, Bailey KR, Klee GG, Ellington AA, Liu G, Rehman H, Kullo IJ. Sex and ethnic differences in 47 candidate proteomic markers of cardiovascular disease: The Mayo Clinic Proteomic Markers of Arteriosclerosis Study. PLoS ONE 2010;5(2):e9065. [PMID: 20140090; PMC2816715].
• Ellington AA, Kullo IJ, Bailey KR, Klee GG. Antibody-based protein multiplex platforms: technical and operational challenges. Clin Chem 2010;56(2):186-93. [PMID: 19959625; PMC2901849].
• Al-Omari MA, Khaleghi M, Mosley TH, Morgenthaler NG, Struck J, Bergmann A, Kullo IJ. Plasma C-terminal pro-endothelin-1 is associated with left ventricular mass index and aortic root diameter in African-American adults with hypertension. J Hum Hypertens. 2011;25(2):106-13. [PMID: 20182452; PMC2921559].
• Noheria A, Mosley TH, Kullo IJ. Association of serum osteoprotegerin with left ventricular mass in African American adults with hypertension. Am J Hypertens. 2010;23(7):767-74. [PMID: 20339356; PMC2901868].
• Saleem U, Mosley TH Jr, Kullo IJ. Serum osteocalcin is associated with measures of insulin resistance and metabolic syndrome. Arterioscler Thromb Vasc Biol 2010;30(7):1474-8. [PMID: 20395593; PMC2939910].
• Ali Z, Ellington AA, Mosley TH Jr, Kullo IJ. Association of serum osteoprotegerin with ankle-brachial index and urine albumin: creatinine ratio in African-Americans and non-Hispanic whites. Atherosclerosis. 2009;206(2):575-580. [PMID: 19423112 ; PMID: 19423112].
• Ellington AA, Kullo IJ, Bailey KR, Klee GG. Measurement and quality control issues in multiplex protein assays: a case study. Clin Chem. 2009;55(6):1092-99. [PMID: 19372187; PMC2965639].
• Saleem U, Khaleghi M, Morgenthaler NG, Bergmann A, Struck J, Mosley TH Jr, Kullo IJ. Plasma carboxy-terminal pro-vasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocr Metab. 2009;94(7):2558-64. [PMID: 19366852; PMC2708945].
• Al-Omari MA, Khaleghi M, Mosley TH, Morgenthaler NG, Struck J, Bergmann A, Kullo IJ. Midregional pro-adrenomedullin is associated with pulse pressure, left ventricular mass, and albuminuria in African American adults with hypertension. Am J Hypertens. 2009;22(8):860-6. [PMID: 19424162; PMC2864024].
• Gerszten RE, Accurso F, Bernard GR, Caprioli RM, Klee EW, Klee GG, Kullo IJ, Laguna TA, Roth RP, Sabatine M, Srinivas P, Wang TJ, Ware LB. Challenges in translating plasma proteomics from bench to bedside: Update from the NHLBI Clinical Proteomics Programs. Am J Physiol Lung Cell Mol Physiol. 2008;295(1):L16-22. [PMID: 18456800; PMC2494793].
• Malik AR, Kondragunta V, Kullo IJ. Forearm vascular reactivity and arterial stiffness in asymptomatic subjects from the community. Hypertension. 2008;51(6):1512-1518. [PMID: 18426995; PMC2869626].
• Kardia SL, Greene MT, Boerwinkle E, Turner ST, Kullo IJ. Investigating the complex genetic architecture of ankle-brachial index, a measure of peripheral arterial disease, in non-Hispanic whites. BMC Med Genomics. 2008;1(1):16. [PMID: 18482449; PMC2412898].
• Khaleghi M, Ali Z, Mosley TH Jr, Turner ST, Kullo IJ. Association of soluble cell adhesion molecules with ankle-brachial index in a biethnic cohort of predominantly hypertensive individuals. Clin Chem. 2008;54:1788-1795. [PMID: 18787016; PMC2752683].
• Roberts RO, Geda YE, Knopman DS, Christianson TJH, Pankratz VS, Boeve BF, Kullo IJ, Rocca WA, Petersen RC. The plasma level of C-reactive protein is associated with mild cognitive impairment. Alzheimer's & Dementia. 2008;4(4)Suppl 1:T298-T299.
• Khaleghi M, Singletary LA, Kondragunta V, Bailey KR, Turner ST, Mosley TH Jr, Kullo IJ. Hemostatic markers are associated with measures of vascular disease in adults with hypertension. J Hum Hypertens. 2009;23(8):530-537. [PMID: 19190656; PMC2712646].
• Khaleghi M, Saleem U, McBane RD, Mosley TH Jr, Kullo IJ. African American ethnicity is associated with higher plasma levels of D-dimer in adults with hypertension. J Thromb Haemost. 2009;7(1):34-40. [PMID: 18983495; PMC2858060].