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Understanding the signaling pathways underlying CH is necessary to identify potential therapeutic targets. The Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchanger isoform I (NHE1), a ubiquitously expressed glycoprotein and cardiac specific isoform, regulates intracellular pH. Recent studies have demonstrated that enhanced expression\/activity of NHE1 contributes to cardiac remodeling and CH. Inhibition of NHE1 in both in vitro and in vivo models have suggested that inhibition of NHE1 protects against hypertrophy. However, clinical trials using NHE1 inhibitors have proven to be unsuccessful, suggesting that additional factors maybe contributing to cardiac remodeling. Recent studies have indicated that the upregulation of NHE1 is associated with enhanced levels of osteopontin (OPN) in the setting of CH. OPN has been demonstrated to be upregulated in left ventricular hypertrophy, dilated cardiomyopathy and in diabetic cardiomyopathy. 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