Osteopontin in Cardiovascular Diseases

Abstract

Unprecedented advances in secondary prevention have greatly improved the prognosis of cardiovascular diseases (CVDs); however, CVDs remain a leading cause of death globally. These findings suggest the need to reconsider cardiovascular risk and optimal medical therapy. Numerous studies have shown that inflammation, pro-thrombotic factors, and gene mutations are focused not only on cardiovascular residual risk but also as the next therapeutic target for CVDs. Furthermore, recent clinical trials, such as the Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial, showed the possibility of anti-inflammatory therapy for patients with CVDs. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions and is involved in a number of pathological states in CVDs. OPN has a two-faced phenotype that is dependent on the pathological state. Acute increases in OPN have protective roles, including wound healing, neovascularization, and amelioration of vascular calcification. By contrast, chronic increases in OPN predict poor prognosis of a major adverse cardiovascular event independent of conventional cardiovascular risk factors. Thus, OPN can be a therapeutic target for CVDs but is not clinically available. In this review, we discuss the role of OPN in the development of CVDs and its potential as a therapeutic target.

Keywords: cardiovascular disease; inflammation; osteopontin.

Figure 1

OPN in cardiac remodeling. OPN is involved in a number of CVDs, including ischemic heart diseases, hypertension, heart failure, dilated cardiomyopathy, atherosclerosis, and several cardiomyopathies and the major source and role of OPN is dependent on pathological states. A number of stimuli are shown to promote OPN expression, including cytokines, ROS, Ang II (angiotensin II), high glucose, hypoxia, and epigenetic mechanisms. Different cell types and pathological states differ in their regulatory mechanisms of OPN in the heart and vessels.

Figure 2

Vicious cycle of OPN in CRS. OPN is involved in the pathogenesis of CRS. Acute or chronic dysfunction of the heart or kidneys can induce OPN expression and may result in acute or chronic dysfunction in the other organ. Several stimuli induce OPN in the pathological conditions of the heart and kidney and OPN causes cardiac fibrosis, cardiac hypertrophy, LV dysfunction, and tubulointerstitial fibrosis.