Right ventricular (RV) failure determines survival and outcome in patients with pulmonary hypertension (PH) of various etiologies. Circulating osteopontin (OPN) levels are elevated in PH patients and correlate with RV dysfunction. We aimed to investigate the expression profile of OPN and its receptors including CD44 and integrins over the course of the development of RV remodeling in mice.
mRNA expression of OPN and its receptors was measured in RV tissues taken from mice, subjected to either sham or pulmonary artery banding (PAB) surgery, at days 3, 7, 14 and 21 post-surgery. OPN localization in RV myocardium of 21-day PAB mice was determined with IHC staining. Plasma levels of OPN were measured using ELISA.
RV OPN mRNA expression was increased at all time-points of PAB. Immunostaining revealed prominent OPN expression in the RV interstitial tissue in PAB mice. Similarly, circulating OPN levels were higher in PAB mice compared to sham mice. mRNA expression of CD44 and integrins including α2, α4, α7, αV, β1, β5 and β8 was increased at earlier time-points of PAB (days 3, 7 and 14). However, at 21 days after PAB, only integrins α2, α4 and β3 remained significantly upregulated, while αV, β1, β5 and β8 expression returned to baseline levels and α7 was downregulated.
RV remodeling in PAB mice is associated with dysregulation of OPN and its receptors CD44 and integrins. However, whether these changes are beneficial or detrimental to the RV remodeling are not known. We are currently conducting studies to investigate the functional role of OPN in pressure overload-induced RV remodeling and dysfunction.