Table 4.

SPARC in cardiac homeostasis and pathophysiology

	Expression	Role
Cardiac homeostasis	Highly expressed in the embryonic heart; expression levels are significantly decreased in the adult myocardium (377)	SPARC contributes to the formation of the collagen network in the adult heart. SPARC null mice have thinner collagen struts. Effects of SPARC deficiency on cardiac function are relatively subtle: SPARC −/− hearts have normal systolic function but exhibit decreased passive stiffness (50), (51).
Cardiac aging	Aging hearts have increased expression of SPARC (51).	Aging SPARC −/− mice have decreased collagen deposition and reduced collagen cross-linking resulting in protection from age-associated diastolic stiffness (51).
Myocardial infarction	SPARC is abundantly expressed in the infarcted myocardium, primarily localized in myofibroblasts and macrophages infiltrating the myocardium (227), (118).	Findings on the role of SPARC in cardiac repair and post-infarction remodelling are somewhat contradictory. Schellings et al found that SPARC upregulation plays an important role in maintaining matrix integrity following myocardial infarction (394). SPARC loss was associated with increased incidence of cardiac rupture due to formation of disorganized granulation tissue and deposition of immature collagen fibers. SPARC overexpression, on the other hand, improved the quality of the scar preventing adverse remodeling. The actions of SPARC were mediated at least in part through enhancement of TGF-β signaling. In contrast, McCurdy et al reported that SPARC null mice had attenuated systolic dysfunction during the early post-infarction phase (289).
Cardiac hypertrophy and fibrosis	SPARC expression is markedly increased in models of cardiac hypertrophy and fibrosis (50).	Much like in the infarct, in the pressure-overloaded myocardium, SPARC regulates matrix remodeling. In a model of pressure overload cardiac fibrosis SPARC null mice have reduced collagen content and attenuated diastolic dysfunction (50).
SPARC in human heart disease	Because of its binding to matrix proteins and growth factors, SPARC appears to have a limited role as a circulating biomarker (404), despite its marked upregulation in the myocardium following cardiac injury.