Early Onset of Chondroitin Sulfate and Osteopontin Expression in Angiotensin II-dependent Left Ventricular Hypertrophy

Background: Chondroitin sulfate proteoglycan (CSPG) is expressed during embryonic heart development and osteopontin (OPN) is an important mediator of the profibrotic effects of angiotensin II (Ang II). The objective of this study was to analyze extracellular matrix protein (ECMP) expression in Ang II-dependent left ventricular (LV) hypertrophy (LVH), LV dysfunction, and to investigate right ventricular changes.

Methods: We used the hypertensive transgenic rat line TGR(mRen2)27 (Ren2), which provides a well-established model of Ang II-driven cardiac remodeling and progressive LV dysfunction and compared young Ren2 rats at the age of 10 weeks with normotensive Sprague-Dawley (SD) rats (n = 15, each group).

Results: Systolic blood pressure and LV weight were elevated in Ren2 compared to SD rats (P < .001). Left ventricular end-diastolic pressure was not altered in Ren2, but +dP/dt(max) and -dP/dt(max) were decreased in Ren2 compared to SD rats (P < .01). Cardiomyocyte widths, interstitial and perivascular fibrosis were increased in left and right ventricles of Ren2 in comparison to SD rats (P < .05). The LV mRNA expression of atrial natriuretic factor, OPN, and collagen I were increased in Ren2 as compared to SD rats (P < .05, respectively). The LV CSPG, collagen I, collagen III, fibronectin, laminin, and OPN contents were elevated in Ren2 compared to SD rats as measured by image analysis and Western blotting (P < .01).

Conclusions: Reactivated expression of CSPG in the adult heart may be an important component of LV ECMP remodeling in LVH. Elevated cardiac OPN expression could mediate the alterations in LV ECMP pattern in Ang II-dependent LVH, thus contributing to the development of contractile dysfunction in young Ren2 rats.