Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Aggrecan accumulates at sites of increased pulmonary arterial pressure in idiopathic pulmonary arterial hypertension

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Contributors:
      Lund University, Faculty of Medicine, Department of Experimental Medical Science, Vessel Wall Biology, Lunds universitet, Medicinska fakulteten, Institutionen för experimentell medicinsk vetenskap, Kärlväggsbiologi, Originator; Lund University, Faculty of Science, Medical Radiation Physics, Lund, Lunds universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik, Lund, Originator; Lund University, Faculty of Engineering, LTH, LTH Profile areas, LTH Profile Area: Engineering Health, Lunds universitet, Lunds Tekniska Högskola, LTH profilområden, LTH profilområde: Teknik för hälsa, Originator; Lund University, Faculty of Science, Medical Radiation Physics, Lund, X-ray Phase Contrast, Lunds universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik, Lund, X-ray Phase Contrast, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Orthopaedics (Lund), Lund OsteoArthritis Division - Molecular marker research group, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Ortopedi, Lund, Lund OsteoArthritis Division - Nedbrytning av ledbrosk: en biologisk process som leder till artros, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Pathology, Lund, Improved diagnostics and prognostics of lung cancer and metastases to the lungs, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Patologi, Lund, Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga, Originator; Lund University, Faculty of Medicine, WCMM-Wallenberg Centre for Molecular Medicine, Lunds universitet, Medicinska fakulteten, WCMM- Wallenberg center för molekylär medicinsk forskning, Originator; Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), eSSENCE: The e-Science Collaboration, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), eSSENCE: The e-Science Collaboration, Originator; Lund University, Faculty of Medicine, Lund University Bioimaging Center, Lunds universitet, Medicinska fakulteten, Lund University Bioimaging Center, Originator; Lund University, Faculty of Medicine, Department of Experimental Medical Science, Lung Biology, Lunds universitet, Medicinska fakulteten, Institutionen för experimentell medicinsk vetenskap, Lungbiologi, Originator
    • نبذة مختصرة :
      Expansion of extracellular matrix occurs in all stages of pulmonary angiopathy associated with pulmonary arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation of the large chondroitin-sulfate proteoglycan aggrecan is associated with swelling and disruption of vessel wall homeostasis. Whether aggrecan is present in pulmonary arteries, and its potential roles in PAH, has not been thoroughly investigated. Here, lung tissue from 11 patients with idiopathic PAH was imaged using synchrotron radiation phase-contrast microcomputed tomography (TOMCAT beamline, Swiss Light Source). Immunohistochemistry for aggrecan core protein in subsequently sectioned lung tissue demonstrated accumulation in PAH compared with failed donor lung controls. RNAscope in situ hybridization indicated ACAN expression in vascular endothelium and smooth muscle cells. Based on qualitative histological analysis, aggrecan localizes to cellular, rather than fibrotic or collagenous, lesions. Interestingly, ADAMTS15, apotential aggrecanase, was upregulated in pulmonary arteries in PAH. Aligning traditional histological analysis with three-dimensional renderings of pulmonary arteries from synchrotron imaging identified aggrecan in lumen-reducing lesions containing loose, cell-rich connective tissue, at sites of intrapulmonary bronchopulmonary shunting, and at sites of presumed elevated pulmonary blood pressure. Our findings suggest that ACAN expression may be an early response to injury in pulmonary angiopathy and supports recent work showing that dysregulation of aggrecan turnover is a hallmark of arterial adaptations to altered hemodynamics. Whether cause or effect, aggrecan and aggrecanase regulation in PAH are potential therapeutic targets.