Abstract
BackgroundIn patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. There is marked heterogeneity in the recruitment of coronary collaterals amongst patients with similar degrees of coronary artery stenoses, but the biological basis of this heterogeneity is not known. Chemokines are potent mediators of vascular remodeling in diverse biological settings. Their role in coronary collateralization has not been investigated. We sought to determine whether plasma levels of angiogenic and angiostatic chemokines are associated with of the presence and extent of coronary collaterals in patients with chronic IHD.Methodology/Principal FindingsWe measured plasma concentrations of angiogenic and angiostatic chemokine ligands in 156 consecutive subjects undergoing coronary angiography with at least one ≥90% coronary stenosis and determined the presence and extent of spontaneously visible coronary collaterals using the Rentrop scoring system. Eighty-eight subjects (56%) had evidence of coronary collaterals. In a multivariable regression model, the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12, hyperlipidemia, and an occluded artery were associated with the presence of collaterals; conversely, the concentration of the angiostatic ligand CXCL11, interferon-γ, hypertension and diabetes were associated with the absence of collaterals (ROC area 0.91). When analyzed according to extent of collateralization, higher Rentrop scores were significantly associated with increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and CXCL11 (p = 0.0002), and interferon-γ (p = 0.0004).Conclusions/SignificancePlasma chemokine concentrations are associated with the presence and extent of spontaneously visible coronary artery collaterals and may be mechanistically involved in their recruitment.
Highlights
Chronic ischemic heart disease (IHD), the most common clinical manifestation of coronary artery disease, results in progressive myocardial ischemia due to gradual narrowing of the coronary arterial lumina and is manifested clinically as medically refractory angina, ischemic cardiomyopathy, congestive heart failure, and cardiac arrhythmias [1]
It is recognized that patients with similar extent and severity of coronary artery disease exhibit marked heterogeneity in the presence and extent of angiographically detectable spontaneous coronary collaterals; this heterogeneity is not explained by traditional cardiac risk factors
Prior studies that examined the role of clinical factors on coronary collateralization have yielded conflicting results: For example, in some studies, diabetes mellitus was found to be a negative predictor of the presence of collaterals [30,31,32,33,34], while in others it was not [35,36,37,38,39]
Summary
Chronic ischemic heart disease (IHD), the most common clinical manifestation of coronary artery disease, results in progressive myocardial ischemia due to gradual narrowing of the coronary arterial lumina and is manifested clinically as medically refractory angina, ischemic cardiomyopathy, congestive heart failure, and cardiac arrhythmias [1]. Recruitable coronary collaterals have been assessed in patients with chronic IHD and are associated with improved clinical outcomes [14]. In patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. Chemokines are potent mediators of vascular remodeling in diverse biological settings Their role in coronary collateralization has not been investigated.
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