Universität zu Köln

Caglayan, Evren, Trappiel, Manuela, Behringer, Arnica, Berghausen, Eva Maria, Odenthal, Margarete, Wellnhofer, Ernst and Kappert, Kai (2019). Pulmonary arterial remodelling by deficiency of peroxisome proliferator-activated receptor- in murine vascular smooth muscle cells occurs independently of obesity-related pulmonary hypertension. Respir. Res., 20. LONDON: BMC. ISSN 1465-993X

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Abstract

BackgroundObesity is associated with cardiovascular complications, including pulmonary hypertension (PH). Reports suggest that peroxisome proliferator-activated receptor- (PPAR) has direct action in preventing vascular remodelling in PH. Here we dissected the specific role of high-fat-diet (HFD)-induced obesity and vascular smooth muscle cell (VSMC)-PPAR for remodelling of small pulmonary arteries.MethodsWild-type (WT) and VSMC-specific PPAR-knockout (SmPpar(-/-)) mice were fed a low-fat-diet (LFD, 10% kcal from fat) or HFD (60% kcal from fat) for 24weeks. Mice were metabolically phenotyped (e.g. weight development, insulin/glucose tolerance) at the beginning, and after 12 and 24weeks, respectively. At 24weeks additionally pulmonary pressure, heart structure, pulmonary vascular muscularization together with gene and protein expression in heart and lung tissues were determined.ResultsHFD increased right ventricular systolic pressure (RVSP) to a similar extent in WT and SmPpar(-/-) mice. HFD decreased glucose tolerance and insulin sensitivity in both WT and SmPpar(-/-) mice. Importantly, the increase in RVSP correlated with the degree of insulin resistance. However, VSMC-PPAR deficiency increased pulmonary vascular muscularization independently of the diet-induced rise in RVSP. This increase was associated with elevated expression of early growth response protein 1 in heart and osteopontin in lung tissue.ConclusionsHere we demonstrate a correlation of insulin resistance and pulmonary pressure. Further, deficiency of PPAR in VSMCs diet-independently leads to increased pulmonary vascular muscularization.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Caglayan, Evren UNSPECIFIED UNSPECIFIED UNSPECIFIED Trappiel, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Behringer, Arnica UNSPECIFIED UNSPECIFIED UNSPECIFIED Berghausen, Eva Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Wellnhofer, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Kappert, Kai UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-156272
DOI:	10.1186/s12931-019-1003-4
Journal or Publication Title:	Respir. Res.
Volume:	20
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1465-993X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SLEEP-APNEA SYNDROME; PPAR-GAMMA; GLUCOSE-INTOLERANCE; EXPRESSION; PATHOGENESIS; INFLAMMATION; OSTEOPONTIN; DYSFUNCTION; INHIBITION; PREVALENCE Multiple languages Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15627