Abstract 19343: Adipose Tissue Renin Angiotensin System in Obstructive Sleep Apnea: Role of Intermittent Hypoxia
Introduction: Obstructive sleep apnea (OSA) is characterized by repetitive nocturnal intermittent hypoxia and is independently associated with cardiovascular diseases, including hypertension. The renin-angiotensin system (RAS) is involved in cardiovascular pathophysiology and is active in adipose tissue. Adipose tissue RAS may significantly contribute to systemic levels of angiotensin II (Ang II), thereby potentiating development of hypertension. However the role of adipose tissue RAS in OSA has not been investigated.
Hypothesize: We hypothesize that apnea-related intermittent hypoxia will stimulate RAS in adipose tissue and contribute to systemically increased Ang II seen in OSA patients.
Methods: We examined the proteins involved in the Ang II generation pathway in adipose tissue of OSA (n=12, age= 44.8 ± 4.3 years, BMI=31.0 ± 2.1 kg/m2) and non-OSA (n=12, age=26.7 ± 1.2 years, BMI= 28.3 ± 1.5 kg/m2) subjects by Western blot analysis. Furthermore, we also examined the effects of intermittent hypoxia on RAS protein in primary cultures of human white preadipocytes (HWP). HWP were exposed to repeated cycles of 30 min-21% O2 (normoxic, n=6) and 30 min-0.1% O2 (hypoxic, n=6) at 37°C for 24 hours. Ang II secretion was also determined by enzyme-linked immunosorbent assay in HWP conditioned medium.
Results: Adipose tissue from OSA subjects showed increased expression of ACE (P=0.04) and chymase (P=0.05), while the expression of renin (P=0.72), AT1R (P=0.53) and AT2R (P=0.80) did not change. In-vitro, intermittent hypoxia upregulated ACE (P=0.04) and chymase (P=0.05) expression while the expression of renin (P=0.94), AT1R (P=0.30), and AT2R (P=0.58) did not change in HWP. Additionally, intermittent hypoxia increased Ang II secretion in HWP (P=0.01).
Conclusions: This is the first study to demonstrate induction of the Ang II generating pathway in OSA adipose tissue. Our data strongly support the role of intermittent hypoxia in upregulating RAS via increases in Ang II. These studies suggest a role for adipose tissue and RAS in OSA related pathophysiology.
Author Disclosures: C. Becari: None. K. Polonis: None. V.K. Somers: None. A.A. Chahal: None. P. Sharma: None. N. Covassin: None. P. Singh: None.
- © 2016 by American Heart Association, Inc.