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Obstructive sleep apnea is a growing worldwide health problem. The landmark feature of OSA is a chronic intermittent hypoxia (CIH) responsible for multiple organ damages including heart diseases. CIH profoundly alters both visceral adipose tissue (VAT) and heart structures and functions, but little is known regarding their interactions in the context of CIH. We recently showed that VAT senescence drives myocardial alterations through the release of profibrotic factors in aged mice. Thus, we aim at demonstrating that CIH induces a premature vWAT senescent phenotype, responsible for subsequent heart dysfunction. In a first series of animals, ten-week old C57BL6 male mice (n = 10/group) were exposed to 14 days CIH protocol (8 hours daily, 5–21% cyclic inspired oxygen fraction, 60 seconds per cycle). In another series, mice were submitted to VAT surgical lipectomy or sham-surgery (n = 10/group) and then exposed to the same CIH protocol. VAT and heart were assessed by histology for fibrosis (Sirius red), cell hypertrophy (wheat-germ agglutinin) and reactive oxygen species (ROS) (4-HNE), and markers of senescence (p16, p21, p53), inflammation (CD68, Tnfa, Serpine1), fibrosis (Col1a1) and hypertrophy were also evaluated by RT-qPCR and western blot. CIH induced an increased macrophage infiltration in VAT, along with an increased expression of senescence markers, ROS production and gene expression of inflammatory and fibrogenic markers. This was associated with CIH-induced myocardial interstitial fibrosis and upregulation of profibrotic gene expression in myocardium. Interestingly, VAT lipectomy prevented CIH-induced myocardial fibrosis. Short-term exposure to CIH is sufficient to induce both VAT remodelling, characterized by oxidative stress, inflammation and fibrosis, and cardiac interstitial fibrosis that was prevented by VAT lipectomy. This strongly suggest a causal crosstalk between CIH-induced VAT senescence and cardiac remodeling. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea is a growing health problem effecting almost 1 billion world population. The landmark feature of OSA is chronic intermittent hypoxia (CIH) responsible for multiple organ damages including heart. CIH profoundly alters both visceral white adipose tissue (vWAT) and heart structures and functions, but little is known regarding their interactions in context of CIH. We recently showed that vWAT senescence drives myocardial alterations through the release of profibrotic factors in aged mice. Here, we aim at demonstrating that CIH induces a premature vWAT senescent phenotype, responsible for subsequent heart dysfunction. In a 1st experiment, 10 weeks old C57BL6 male mice (n = 10/group) were exposed to 14 days CIH protocol (8 hours daily, 5-21% cyclic inspired oxygen fraction, 60 seconds per cycle). In a 2nd series, mice were submitted to either vWAT lipectomy or sham-surgery. Finally, we used p53 KO mice or littermates, also exposed to the same CIH protocol. vWAT and hearts were assessed for fibrosis, hypertrophy, DNA damage, oxidative stress, markers of senescence (p16, p21, p53) and inflammation by histology, RT-qPCR and western blot. CIH induced a "senescent-like" phenotype in vWAT, characterized by increased fibrosis, oxidative stress, DNA damage and inflammation (macrophage infiltration and inflammatory markers expression). This was associated with CIH-induced myocardial interstitial fibrosis and upregulation of profibrotic gene expression in myocardium. Interestingly, CIH did not induce vWAT remodeling in p53KO mice and CIH-induced myocardial interstitial fibrosis was prevented by both vWAT resection and p53 deletion. Short-term exposure to CIH is sufficient to induce vWAT premature senescence and cardiac interstitial fibrosis that was prevented by vWAT lipectomy and deletion of p53 senescence pathway. This strongly suggest a causal crosstalk between CIH-induced vWAT senescence and cardiac remodelling. [ABSTRACT FROM AUTHOR]