Abstract
BackgroundCardiac stem cells (CSCs) play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR) was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated.MethodsTo examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR) treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day) for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats.ResultsFunctional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment.DiscussionAs anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of healthy stem cell population is suggested as a possible mechanism underlying the cardioprotective effect of famotidine.
Highlights
The discovery of cardiac stem cells challenged the notion of heart being a post-mitotic organ (Beltrami et al, 2003)
Cardiomyocyte turnover ranges from 0.5–1% annually (Bergmann et al, 2009), implicating the involvement of cardiac stem cells in the maintenance of cardiac homeostasis
We have reported that the H2 receptor antagonist famotidine promotes reverse cardiac remodeling in spontaneously hypertensive rats (SHRs) (Potnuri et al, 2016)
Summary
The discovery of cardiac stem cells challenged the notion of heart being a post-mitotic organ (Beltrami et al, 2003). In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR) was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR) treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were reduced. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of healthy stem cell population is suggested as a possible mechanism underlying the cardioprotective effect of famotidine
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