Premium
Intermittent Hypoxia Upregulates Angiotensin II Generating Pathways in Human Preadipocytes
Author(s) -
Becari Christiane,
Singh Prachi,
Polonis Katarzyna,
Somers Virend K.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.765.6
Subject(s) - chymase , endocrinology , adipose tissue , medicine , angiotensin ii , renin–angiotensin system , hypoxia (environmental) , intermittent hypoxia , white adipose tissue , downregulation and upregulation , angiotensin ii receptor type 1 , angiotensin converting enzyme , receptor , chemistry , biology , obstructive sleep apnea , enzyme , blood pressure , biochemistry , gene , organic chemistry , oxygen
Background Obstructive sleep apnea (OSA) is characterized by repetitive intermittent hypoxia and reoxygenation during sleep, and is a risk factor for cardiometabolic diseases including hypertension and diabetes. The renin‐angiotensin system (RAS) is an important cardiovascular and metabolic regulator playing key roles via angiotensin peptides. Recent studies demonstrate that all components of the RAS, including enzymes responsible for AngII generation, such as angiotensin converting enzyme (ACE) and chymase, are present in adipose tissue. Furthermore adipose tissue significantly contributes to systemic levels of AngII, thereby potentiating development of hypertension in obesity. Given that OSA patients are mostly obese, the localized effects of RAS in adipose tissue are likely an important mediator of OSA‐related hypertension. This study sought to investigate the effects of intermittent hypoxia (IH), a hallmark of OSA, on Ang II generation pathways in preadipocytes. Methods/Results RAS plays an important role in adipose tissue via its action on preadipocytes. Therefore, we examined the effects of IH in primary cultures of human white preadipocytes (HWP). HWP cells were exposed to repeated cycles of 30 min‐21% O 2 (normoxic) and 30 min‐1% O 2 (hypoxic) at 37°C for 24 hours. Cells grown in continuous normoxic conditions were used as controls. mRNA and protein expression of ACE, chymase, renin, AT1, and AT2 receptors were investigated by semi‐quantitative RT‐PCR and Western blot, respectively. Ang II secretion was examined by enzyme‐linked immunosorbent assay in condition medium. Results IH 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) receptors did not change in HWP. Additionally, IH increased Ang II secretion in conditioned media (P=0.01). Conclusions This is the first study to demonstrate intermittent hypoxia‐mediated upregulation of Ang II generating enzymes ACE and chymase, along with increased AngII secretion in HWP. Together, our data strongly support the role of IH in upregulating RAS via increases in AngII. These studies suggest a role for adipose tissue and RAS in OSA related pathophysiology. Support or Funding Information NIH R01 grant (#HL65176); Becari C. is supported by grant from CNPq‐Brazil (# 203802/2014‐4).