title: Chronic and intermittent hypoxia differentially regulate left ventricular inflammatory and extracellular matrix responses.
abstract: We evaluated the left ventricle (LV) response to hypoxia by comparing male Sprague Dawley rats exposed for 7 days to normoxia (control; n=18), chronic sustained hypoxia (CSH; n=12) and chronic intermittent hypoxia (CIH; n=12). Out of the 168 inflammatory, extracellular matrix and adhesion molecule genes evaluated, Ltb, Cdh4, Col5a1, Ecm1, MMP-11 and TIMP-2 increased in the LV (range: 87-138%), whereas Tnfrsf1a decreased 27%, indicating an increase in inflammatory status with CSH (all P<0.05). CIH decreased Ltb, Spp1 and Ccl5 levels, indicating reduced inflammatory status. While Laminin β2 gene levels increased 123%, MMP-9 and fibronectin gene levels both decreased 74% in CIH (all P<0.05). Right ventricle/body weight ratios increased in CSH (1.1±0.1 g g(-1)) compared with control (0.7±0.1 g g(-1)) and CIH (0.8±0.1 g g(-1); both P<0.05). Lung to body weight increased in CSH, while LV/body weight ratios were similar among all three groups. With CIH, myocyte cross sectional areas increased 25% and perivascular fibrosis increased 100% (both P<0.05). Gene changes were independent of global changes and were validated by protein levels. MMP-9 protein levels decreased 94% and fibronectin protein levels decreased 42% in CIH (both P<0.05). Consistent with a decreased inflammatory status, HIF-2α and eNOS protein levels were 36% and 44% decreased, respectively, in CIH (both P<0.05). In conclusion, our results indicate that following 7 days of hypoxia, inflammation increases in response to CSH and decreases in response to CIH. This report is the first to demonstrate specific and differential changes seen in the LV during chronic sustained and CIH.
authors.affiliation: Barshop Institute of Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
authors.forename: Trevi A
authors.initials: TA
authors.lastname: Ramirez
authors.forename: Claude
authors.initials: C
authors.lastname: Jourdan-Le Saux
authors.forename: Anne
authors.initials: A
authors.lastname: Joy
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Dai
authors.forename: Steve
authors.initials: S
authors.lastname: Mifflin
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology*; D015870:Gene Expression / Q000235:genetics; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators