Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice

Abstract

We have reported previously that intermittent hypoxia related to sleep apnea induces cardiovascular remodeling secondary to the oxidative stress. The aim of this study was to examine the effect of pitavastatin as an antioxidant to prevent intermittent hypoxia-induced left ventricular (LV) remodeling in mice without hypercholesterolemia. Eight-week-old male C57BL/6J mice (n¼35) were exposed to intermittent hypoxia (30 s exposure to 5% oxygen, followed by 30 s exposure to 21% oxygen) for 8 h per day during the daytime or maintained under normoxic conditions; in addition, they were either treated with pitavastatin (3 mg kg À1 per day) or vehicle for 10 days. After cardiac catheterization and blood sampling, the LV myocardium was examined. The systemic blood pressure and plasma level of total cholesterol were similar among the four groups. Intermittent hypoxia significantly increased the expression levels of 4-hydroxy-2-nonenal (4-HNE) proteins, TNF-a and TGF-b mRNA, and also the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL)-positive myocardial cells in the LV myocardium. In addition, enhanced hypertrophy of the cardiomyocytes, perivascular fibrosis and histological degeneration were observed in the mice exposed to hypoxic stress. Treatment with pitavastatin significantly suppressed the expression levels of the 4-HNE proteins, cytokines, superoxide production and TUNEL-positive myocardial cells in the LV myocardium, consequently attenuating the hypoxia-induced histological changes. Pitavastatin preserved, at least partially, the morphological structure of the LV myocardium in lean mice exposed to intermittent hypoxia, through its antioxidant effect.

Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia

“…Then tumor necrosis factor-α (TNF-α and brain natriuretic peptide (BNP) mRNA were detected by performing RT-PCR under the following conditions: 50C for 2 min, 95C for 10 min, 40 cycles of 95C for 15 s, and 60C for 1 min. Expression of the target mRNAs was normalized for that of GAPDH mRNA (Inamoto et al, 2010).…”

“…We previously demonstrated that chronic hypoxia accelerates the progression of atherosclerosis in apoE-KO mice Kato R, et al Ezetimibe and Cardiovascular Protection 6 (Nakano et al, 2005), while statin therapy reduces oxidative stress and attenuates left ventricular remodeling induced by intermittent hypoxia in mice (Inamoto et al, 2010).…”

Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters

“…Negative controls were processed with distilled water, and endometrium was used as the positive control. After cells were counterstained with Mayer's hematoxylin, TUNEL-positive cells were counted as described elsewhere (15).…”

Not sleeping well can damage your heart

“…A recent study showed that central obesity without OSA was not correlated with endothelial dysfunction, inflammation and increased oxidative stress. 9,10 There is a strong correlation between the extent of endothelial dysfunction and the severity of OSA. This is supported by evidence that OSA itself, but not obesity, induces vascular endothelial dysfunction and inflammation and also elevates oxidative stress (see Figure 1).…”

“…2 Although co-founding variables made it difficult to directly link OSA and left ventricular hypertrophy, a close relationship between these two pathological conditions could dramatically and negatively impact patients' prognoses; therefore, molecular mechanisms that could establish a causal relationship between OSA and left ventricular hypertrophy should be more extensively studied. In this issue of Hypertension Research, Inamoto et al 10 examined the effects of statin therapy on intermittent hypoxia-induced left ventricular remodeling in mice, a known model for OSA. They reported that intermittent hypoxia-induced hypertrophy of the cardiomyocytes led to perivascular fibrosis and histological degeneration without affecting systemic blood pressure or plasma cholesterol.…”