Biomarkers for Cardiovascular Disease

Source MDx has selected over 400 candidate target genes for the future development of Precision Profiles™ in Cardiovascular Disease. These target gene assays have been selected through independent literature review and in collaboration with our pharmaceutical and academic partners. Precision Profiles™ in Cardiovascular Disease are intended to measure whole blood and circulating endothelial cell (CEC) gene expression responses in a range of disorders affecting the heart and/or peripheral blood vessels including coronary artery disease (atherosclerosis), heart attack (myocardial infarction), heart failure, high blood pressure and stroke. Furthermore, Precision Profiles™ in Cardiovascular Disease will also include an additional 250 inflammation and immune response-related genes reflecting the impact of inflammatory processes that have a demonstrated association with cardiovascular disease.

Clinical Studies in Cardiovascular Disease

Source MDx is currently working in collaboration with Dr. Michael Mendelsohn, head of the Molecular Cardiology Research Institute at Tufts Medical Center, in the future development of our cardiovascular disease program.

To date, preliminary work in this area includes a recently completed, Source MDx funded study in the enumeration of circulating endothelial cells in 300 healthy blood bank donors. This served to establish a range of expected CEC counts across a healthy blood bank donor population. Additional companion samples were also collected for the enrichment of CEC’s providing the opportunity for downstream gene expression characterization of CECs in this population of normal subjects. In these efforts, Source MDx utilized the Veridex Cell Search System™ in conjunction with the CellSearch™ CEC detection kit to isolate, enumerate and enrich CECs from whole blood. This foundational work is anticipated to provide molecular insights into the role of CECs in subjects afflicted with cardiovascular disease versus healthy normal subjects.

Link between Inflammation and Cardiovascular Disease

Source MDx intends to pursue the cardiovascular specific and the more general pro-inflammatory components in the characterization of numerous cardiovascular disorders, as the link between chronic inflammation and the disruption of coordinated function of key cell types influencing cardiovascular health is well described in the literature. Some select references are provided below.

• Celis R et al. Evidence for activation of immune system in heart failure: is there a role for anti-inflammatory therapy? Curr Opin Cardiol. 2008 May;23(3):254-60.
• Croce K et al. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol. 2007 Jan;14(1):55-61.
• Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006 Apr 18;47(8 Suppl):C7-12.
• Fan J et al. Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb. 2003;10(2):63-71.
• Forrester JS et al. The inflammation hypothesis and its potential relevance to statin therapy. Am J Cardiol. 2007 Mar 1;99(5):732-8. Epub 2007 Jan 10.
• Góis J et al. Infectious agents, inflammation, and growth factors: how do they interact in the progression or stabilization of mild human atherosclerotic lesions? Ann Vasc Surg. 2006 Sep;20(5):638-45. Epub 2006 Sep 17.
• Hansson GK et al. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006 Jul;6(7):508-19. Epub 2006 Jun 16.
• Huang J et al. Inflammation in stroke and focal cerebral ischemia. Surg Neurol. 2006 Sep;66(3):232-45.
• Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006 Feb;83(2):456S-460S.
• Libby P. Inflammation in atherosclerosis. Nature. 2002 Dec 19-26;420(6917):868-74.
• Libby P et al. Inflammation and thrombosis: the clot thickens. Circulation. 2001 Apr 3;103(13):1718-20.
• Libby P et al. Pathophysiology of coronary artery disease. Circulation. 2005 Jun 28;111(25):3481-8.
• Lombardo A et al. Inflammation as a possible link between coronary and carotid plaque instability. Circulation. 2004 Jun 29;109(25):3158-63. Epub 2004 Jun 7.
• Loppnow H et al. Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity-related inflammatory mechanisms. Innate Immun. 2008 Apr;14(2):63-87.
• Packard RR et al. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008 Jan;54(1):24-38.
• Ray KK et al. Pathological changes in acute coronary syndromes: the role of statin therapy in the modulation of inflammation, endothelial function and coagulation. J Thromb Thrombolysis. 2004 Oct;18(2):89-101.
• Rodríguez-Yáñez M et al. Role of inflammatory markers in brain ischemia. Curr Opin Neurol. 2008 Jun;21(3):353-7.
• Stoll G et al. Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke. 2006 Jul;37(7):1923-32. Epub 2006 Jun 1.
• Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol. 2005 Jun 6;95(11A):3C-8C; discussion 38C-40C.
• Welsh P et al. Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke. 2008 Aug;39(8):2226-30. Epub 2008 Jun 19.
• Yan ZQ et al. Innate immunity, macrophage activation, and atherosclerosis. Immunol Rev. 2007 Oct;219:187-203.