The association of interferon‐alpha with development of collateral circulation after artery occlusion

Abstract

Background: Previous studies have demonstrated that interferon (IFN) signaling is enhanced in patients with poor collateral circulation (CC). However, the role and mechanisms of IFN-alpha in the development of CC remain unknown. Methods:We studied the serum levels of IFN-alpha and coronary CC in a casecontrol study using logistics regression, including 114 coronary chronic total occlusion (CTO) patients with good coronary CC and 94 CTO patients with poor coronary CC. Restricted cubic splines was used to flexibly model the association of the levels of IFN-alpha with the incidence of good CC perfusion restoration after systemic treatment with IFN-alpha was assessed in a mice hind-limb ischemia model. Results:Compared with the first IFN-alpha tertile, the risk of poor CC was higher in the third IFN-alpha tertile (OR: 4.79, 95% CI: 2.22-10.4, p < .001). A cubic spline-smoothing curve showed that the risk of poor CC increased with increasing levels of serum IFNalpha. IFN-alpha inhibited the development of CC in a hindlimb ischemia model. Arterioles of CC in the IFN-alpha group were smaller in diameter than in the control group. Conclusion: Patients with CTO and with poor CC have higher serum levels of IFNalpha than CTO patients with good CC. IFN-alpha might impair the development of CC after artery occlusion. K E Y W O R D S collateral circulation, coronary chronic total occlusion, IFN-alpha 1 | BACKGROUND Development of collateral circulation (CC), also termed as arteriogenesis, is a natural life-preservation mechanism occurring in patients with coronary chronic total occlusion (CTO). Well-developed CC preserves cardiac function, thus reducing cardiac mortality after coronary occlusion. 1,2 Patients with CTO show a great deal of heterogeneity in their arteriogenic responses to artery occlusion. This is affected by multiple factors, including inflammatory factors. 3 The