Coronary artery disease (GAD) remains the leading cause of morbidity and mortality in the western world. Chronic, progressive worsening of an arterial stenosis can lead to complete occlusion of the coronary artery resulting in adverse clinical outcomes. In many patients with chronic ischemic heart disease (IHD), however, compensatory mechanisms that limit myocardial ischemia and preserve cardiac function (even in the presence of a complete arterial occlusion) can occur: patients in whom the robust formation of new capillaries (angiogenesis) and/or the formation of collateral arterial supply (arteriogenesis) occurs have markedly better cardiac function and clinical outcomes when compared to patients where the angiogenesis/arteriogenesis is limited or nonexistent. A striking, but mechanistically unexplained, clinical observation is that patients with similar degrees of coronary stenosis and myocardial ischemia have markedly heterogenous extent of myocardial neovascularization. Chemokines, a superfamily of cytokines originally described for their role in mediating leukocyte recruitment to sites of inflammation, have been established as important mediators of angiogenesis and arteriogenesis in diverse disease settings. A unique feature of chemokines is that while some are potent promoters of neovascularization, others are potent inhibitors. To date, very little is known regarding the role of chemokines in chronic IHD. Our overall hypothesis is that the relative balance of angiogenic and angiostatic chemokines contributes to neovascularization of the myocardium in patients with chronic IHD. We propose to test this hypothesis in a highly characterized population of chronic IHD patients undergoing coronary angiography under the following Spiecific Aims: (1) To correlate the presence and extent of myocardial neovascularization in patients with chronic IHD undergoing coronary angiography with their circulating levels of angiogenic and angiostatic chemokines;(2) To determine the frequency of genetic polymorphisms in angiogenic and angiostatic chemokines associated with myocardial neovascularization in a highly characterized population of chronic IHD patients undergoing coronary angiography;and (3) To assess the predictive value of angiogenic and angiostatic chemokines as biomarkers of future adverse cardiac events in patients with chronic IHD.
The relevance of this proposal is that it will elucidate the mechanism(s) of the clinically important but incompletely understood problem of neovascularization of the ischemic myocardium. Its innovation is that it has the potential to link the well-characterized mechanism of chemokine- mediated vascular remodeling to ischemic heart disease, and ultimately result in novel diagnostic and therapeutic applications.
|Loguidice, Michael J; Schutt, Robert C; Horton, Jureta W et al. (2016) Heart Rate Variability as a Predictor of Death in Burn Patients. J Burn Care Res 37:e227-33|
|Keeley, Ellen C; Schutt, Robert C; Marinescu, Mark A et al. (2016) Circulating fibrocytes as predictors of adverse events in unstable angina. Transl Res 172:73-83.e1|
|Kuruvilla, Sujith; Janardhanan, Rajesh; Antkowiak, Patrick et al. (2015) Increased extracellular volume and altered mechanics are associated with LVH in hypertensive heart disease, not hypertension alone. JACC Cardiovasc Imaging 8:172-80|
|Kloepfer, Angela M; Lipson, Lewis C; Keeley, Ellen C (2014) The presence of angiographic collaterals in non-ST elevation myocardial infarction is a predictor of long-term clinical outcomes. Catheter Cardiovasc Interv 83:1-8|
|Naik, Bhiken I; Keeley, Ellen C; Gress, Daryl R et al. (2014) Case scenario: a patient on dual antiplatelet therapy with an intracranial hemorrhage after percutaneous coronary intervention. Anesthesiology 121:644-53|
|Schutt, Robert C; Young, Shiu M; Liu, Ling et al. (2014) The association of angiographic collaterals with long-term clinical outcomes in patients with chronic stable angina. J Interv Cardiol 27:225-32|
|Keeley, Ellen C; Mehran, Roxana; Brener, Sorin J et al. (2014) Impact of multiple complex plaques on short- and long-term clinical outcomes in patients presenting with ST-segment elevation myocardial infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-A Am J Cardiol 113:1621-7|
|Jones, Robert M; Enfield, Kyle B; Mehrad, Borna et al. (2014) Prevalence of obstructive coronary artery disease in patients undergoing lung transplantation: case series and review of the literature. Catheter Cardiovasc Interv 84:1-6|
|Dietz, Denise M; Cleveland, John D; Chewning, Kelly G et al. (2013) Impending paradoxical embolism presenting as myocardial infarction. J Cardiol Cases 7:e145-e148|
|Keeley, Ellen C; Mehrad, Borna; Kramer, Christopher M (2013) Response to Van Koppen et al. J Hypertens 31:1054-5|
Showing the most recent 10 out of 27 publications