Chronic intermittent hypoxia exacerbates isoproterenol-induced cardiac hypertrophy and apoptosis

TL;DR

Chronic intermittent hypoxia worsens heart enlargement and cell death caused by isoproterenol in mice and heart cells.

Contribution

This study reveals that CIH intensifies ISO-induced cardiac hypertrophy and apoptosis through activation of the PI3K/AKT/mTOR pathway.

Findings

CIH worsens ISO-induced cardiac dysfunction and pathological changes in mice.

CIH increases expression of ANP and BNP in mice and H9C2 cells.

CIH aggravates ISO-induced cardiomyocyte apoptosis and activates the PI3K/AKT/mTOR pathway.

Abstract

Obstructive sleep apnea (OSA) is marked by chronic intermittent hypoxia (CIH) and iassociated with multiple cardiovascular complications. Isoproterenol (ISO) is commonly used to induce cardiac hypertrophy. However, the impact of CIH on ISO-induced cardiac hypertrophy and remodeling remains unclear.

Cardiac hypertrophy was induced in mice using ISO, with or without CIH. Echocardiography was performed to assess cardiac functions, while histological analyses were employed to evaluate the physiological modifications in the heart. Western blotting and real-time quantitative PCR were used to evaluate protein and mRNA gene expression levels, respectively. Additionally, immunofluorescence was employed to observe the morphological changes in H9C2 cells.

CIH exacerbated ISO-induced cardiac dysfunction and cardiac pathological alterations in mice. The expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was elevated in both mice and H9C2 cells in the CIH + ISO group. Furthermore, CIH exacerbated ISO-induced cell apoptosis. We additionally observed that the PI3K/AKT/mTOR pathway is further activated by the co-induction of CIH and ISO.

CIH exhibits a negative effect on ISO-treated mice and cells, leading to an exacerbation of cardiac dysfunction and remodeling. In addition, CIH aggravates ISO-treated cardiomyocyte apoptosis in H9C2 cells.

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