Pulmonary arterial remodelling by deficiency of peroxisome proliferator-activated receptor-γ in murine vascular smooth muscle cells occurs independently of obesity-related pulmonary hypertension

Respiratory Research
Evren CaglayanKai Kappert

Abstract

Obesity is associated with cardiovascular complications, including pulmonary hypertension (PH). Reports suggest that peroxisome proliferator-activated receptor-γ (PPARγ) 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)-PPARγ for remodelling of small pulmonary arteries. Wild-type (WT) and VSMC-specific PPARγ-knockout (SmPparγ-/-) mice were fed a low-fat-diet (LFD, 10% kcal from fat) or HFD (60% kcal from fat) for 24 weeks. Mice were metabolically phenotyped (e.g. weight development, insulin/glucose tolerance) at the beginning, and after 12 and 24 weeks, respectively. At 24 weeks additionally pulmonary pressure, heart structure, pulmonary vascular muscularization together with gene and protein expression in heart and lung tissues were determined. HFD increased right ventricular systolic pressure (RVSP) to a similar extent in WT and SmPparγ-/- mice. HFD decreased glucose tolerance and insulin sensitivity in both WT and SmPparγ-/- mice. Importantly, the increase in RVSP correlated with the degree of insulin resistance. However, VSMC-PPARγ deficiency increased pulmonary vascular muscularization independently o...Continue Reading

References

Apr 3, 2008·The Journal of Clinical Investigation·Georg HansmannMarlene Rabinovitch
Jul 4, 2008·The Journal of Clinical Investigation·Marlene Rabinovitch
Sep 16, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Brian Fouty
Nov 26, 2008·Chronic Respiratory Disease·A T Murugan, G Sharma
Dec 3, 2008·The European Respiratory Journal·R T ZamanianR L Doyle
Jun 13, 2009·American Journal of Respiratory Cell and Molecular Biology·Rachel E NisbetC Michael Hart
Apr 8, 2010·Science Translational Medicine·Georg Hansmann, Roham T Zamanian
Sep 19, 2012·Journal of Obesity·Scott E Friedman, Bruce W Andrus
Oct 23, 2012·Journal of the American Society of Nephrology : JASN·Hiromi TachibanaHirofumi Makino
Jun 22, 2014·Circulation Research·Evangelos D Michelakis
Jun 22, 2014·Circulation Research·Marlene RabinovitchMark R Nicolls
Mar 7, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Henrik Ten FreyhausStephan Rosenkranz
Apr 2, 2015·Molecular Metabolism·Janine KrügerKai Kappert
Jan 9, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Arnica BehringerEvren Caglayan
Jan 18, 2016·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Diederik E van der FeenRolf M F Berger
Jul 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Mirna SakerSerge Adnot
Jan 25, 2017·American Journal of Respiratory Cell and Molecular Biology·Qingqing MengMark T Gladwin
May 6, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Jolyane MelocheSébastien Bonnet
Apr 27, 2018·Science Translational Medicine·Ekaterina LegchenkoGeorg Hansmann
May 11, 2018·Respiratory Research·Hang YangZhou Zhou
Oct 7, 2018·Current Hypertension Reports·Karnika AyinapudiSuzanne Oparil

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

Cell D Imaging
LabChart7®
SPSS

Related Concepts

Related Feeds

CFTR Mutant Structural Therapy

Over 1700 different mutations in the CFTR genes have been shown to cause cystic fibrosis. Here is the latest research on structural therapy for CFTR mutants.

Cardiovascular Diseases: Risk Factors

Cardiovascular disease is a significant health concern. Risk factors include hypertension, obesity, dyslipidemia and smoking. Women who are postmenopausal are at an increased risk of heart disease. Here is the latest research for risk factors of cardiovascular disease.