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Updated: Apr 26, 2026

A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats
Published on: March 1, 2022
Pulmonary hypertension is related to peripheral endothelial dysfunction in heart failure with preserved ejection
Marta Farrero1, Isabel Blanco2, Montserrat Batlle2
1From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain. mfarrero@clinic.ub.es.
Background:
Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF.;
Methods And Results:
Flow-mediated dilation of the brachial artery, matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C-terminal propeptide of type I procollagen were determined in 28 patients with HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery pressure >35 mm Hg on echocardiogram underwent a right heart catheterization. Patients with HFpEF had more severe PED than controls: flow-mediated dilation 1.95% (-0.81 to 4.92) versus 5.02% (3.90 to 10.12), P=0.002. Twenty patients with PH underwent right heart catheterization: mean pulmonary artery pressure 38 (27-52) mm Hg, wedge capillary pressure 18 (16-22) mm Hg, pulmonary vascular resistance 362 (235-603) dyn s cm(-5). There was a significant inverse correlation between flow-mediated dilation and pulmonary vascular resistance in patients with HFpEF and PH (r=-0.679; P=0.002). Patients with HFpEF showed higher matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide of type I procollagen values also had higher mean pulmonary artery pressure (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary vascular resistance (r=0.626; P=0.004).
Conclusions:
In patients with HFpEF, there is a significant correlation between PED and pulmonary vascular resistance. Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify patients with HFpEF at risk of developing PH.
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