The Toll way to hypertension: role of the innate immune response

Abstract

The involvement of pro-inflammatory processes in cardiovascular disease such as hypertension is a well accepted concept. Human hypertension is associated with increased levels of circulating cytokines and their participation in the associated target organ damage has clearly been demonstrated. Recent evidence suggests that at least in animal models of hypertension, components of the adaptive immune system such as T cells are activated and infiltrate target organs, promoting inflammation and thus participating in the maintenance of increased blood pressure. However there is a paucity of information on the role of the innate immune response in hypertension. Moreover, the identity of the original stimuli responsible for the immune system activation as well as the chronology of these events during hypertension pathogenesis is unknown. The current paradigm is that the immune system is activated by danger signals originating from stressed or injured cells and tissues which release molecules (damage-associated molecular patterns or DAMPs) recognized by pattern recognition receptors, such as Toll like receptors, on antigen-presenting cells (APCs). APCs in turn activate the adaptive immune response and both kinds of response will lead to release of pro-inflammatory factors, such as cytokines and chemokines. During hypertension, cytokine/chemokine signaling in the kidney and vasculature may cause further injury and release of DAMPs continuously, resulting in a sustained chronic inflammatory process. In the present review, we describe recent research supporting the hypothesis of the immune system activation as a causative factor of hypertension, with a special focus on the involvement of the innate immune response in the initiation of hypertension and the hypertensive vascular and renal dysfunction.