The goals of our work are to improve understanding of inflammatory processes in the heart and the role of inflammatory mediators on cardiac function.
Cytokines and their receptors play central roles in regulating inflammation; however, these peptides also have biological effects independent of their impact on leukocyte activation and trafficking which includes effects on the heart. More recently, a role for chemokines, cytokines with potent chemoattractant properties, and their receptors has been implicated in the pathogenesis of several cardiovascular disorders (atherosclerosis, myocardial failure). In concert with cytokines, chemokines likely contribute to cardiovascular and cardiac disease observed during chronic disease conditions having increased immune activation (e.g. HIV, atherosclerosis, and obesity) but their relative contributions and mechanisms are not well characterized. Our lab research is directed at defining the contribution of chemokines in cardiac dysfunction. We hypothesize that the inflammatory milieu that accompanies many chronic diseases can induce cardiac dysfunction.
Similar to the pro-inflammatory cytokines, myocardial depressant effects or attenuation of β-adrenergic signaling have been reported downstream of the chemokine receptors (CXCR4, CX3CR1, CCR5) whose expression has been described in cardiomyocytes thus far. In the heart, the chemokine receptors have been reported to have impacts on cardiac development (CXCR4, CX3CR1), inflammation and repair after myocardial infarction (CCR2, CXCR4, CCR5), heart failure (CXCR4, CCR2), myocarditis (CX3CR1), and diastolic dysfunction (CCR5). Although the role of chemokines and their receptors in many cardiac diseases is often attributed to attenuation of the immune response, there may also be an unrecognized direct role.
We seek to define the pathways triggered by chemokines and the mechanisms that result in altered myocardial contractility. Little is known about the in vivo effects of chemokines, and we will also explore the possibility of additive effects of these chemokines on cardiac function, together with pro-inflammatory cytokines, and evaluate for redundant pathways and potential therapeutic targets.