title: Abnormal Remodeling of Subcutaneous Small Arteries Is Associated With Early Diastolic Impairment in Metabolic Syndrome.
abstract: BACKGROUND
  Small artery pathophysiology is frequently invoked as a cause of obesity-related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans.
  
  
  RESULTS
  To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelial dysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (β=0.718,P=0.02) and wall-to-lumen ratio (β=0.605,P=0.02). Furthermore, the E:E' ratio was associated with wall-to-lumen ratio (β=0.596,P=0.02) and inversely associated with interleukin-6 (β=-0.868,P=0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied.
  
  
  CONCLUSIONS
  Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment.
authors.affiliation: Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.|British Heart Foundation Centre of Excellence, The Rayne Institute, King's College London, London, United Kingdom.
authors.forename: Kaivan
authors.initials: K
authors.lastname: Khavandi
authors.affiliation: Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Reza
authors.initials: R
authors.lastname: Aghamohammadzadeh
authors.affiliation: Manchester Heart Centre, Central Manchester Teaching Hospitals Foundation Trust, Manchester, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Luckie
authors.affiliation: St. George's Vascular Institute, St George's, University of London, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Brownrigg
authors.affiliation: Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Uazman
authors.initials: U
authors.lastname: Alam
authors.affiliation: Department of Cardiology, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Rajdeep
authors.initials: R
authors.lastname: Khattar
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Doha, Qatar.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.affiliation: Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
authors.affiliation: Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom adam.greenstein@manchester.ac.uk.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Greenstein
mesh_terms: D000328:Adult; D000368:Aged; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D002081:Buttocks; D016022:Case-Control Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D006801:Humans; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000503:physiopathology*; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000098:blood supply*; D066253:Vascular Remodeling; D014664:Vasodilation; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016277:Ventricular Function, Left
keywords: diastolic dysfunction; endothelial dysfunction; heart failure; obesity; vascular remodeling