Plasma ratio of angiopoietin-2 to angiopoietin-1 is a biomarker of vascular impairment in chronic obstructive pulmonary disease patients

Fares Gouzi (1, 2, 3) , Aurélien Philippe (3, 4) , Léo Blervaque (5) , Sven Günther (3, 4) , Anne Virsolvy (1, 2) , Maxime Gruest (3, 4) , Olivier Cazorla (1, 2) , Elisa Rossi (3) , David M. Smadja (3, 4)

1 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 LIBM - Laboratoire Interuniversitaire de Biologie de la Motricité

Chronic obstructive pulmonary disease (COPD) patients have an increased risk of cardiovascular disease. Muscle biopsies have revealed that the muscle vasculature in COPD patients was characterized by a capillary rarefaction with reduced pericyte coverage. Thus, an imbalance of the plasma Angiopoietin-1 / Angiopoietin-2 (Ang2/Ang1) ratio could constitute a non-invasive marker of the muscle vascular impairment. In 14 COPD patients (65.5±5.1-year-old) and 7 HC (63.3±5.8-year-old), plasma samples were obtained at 3 time-points: before, after 5 weeks (W5), and after 10 weeks (W10) of exercise training. COPD patients showed a muscle capillary rarefaction at baseline with a reduced capillary coverage at W5 and W10. The plasma Ang2/Ang1 ratio was significantly higher in COPD patients vs. HC during the training (Group: p=0.01). The plasma Ang2/Ang1 ratio was inversely correlated with the pericyte coverage index regardless of the time period W0 (r=−0.51; p=0.02), W5 (r=−0.48; p=0.04), and W10 (r=−0.61; p<0.01). Last, in ECFC/MSC co-cultures exposed to the W10 serum from COPD patients and HC, the plasma Ang2/Ang1 at W10 were inversely correlated with calponin staining (r=−0.64. p=0.01 and r= 0.71. p<0.01, Fig. 1B), in line with a role of this plasma Ang2/Ang1 in the MSC differentiation into pericytes. Altogether, plasma Ang2/Ang1 ratio could constitute a potential marker of the vascular impairment in COPD patients.

Mots clés: Angiopoietins; COPD; Pericyte; Vessels; Cardiopulmonary exercise test; V’O2max

Domaines: Pneumologie et système respiratoire; Cardiologie et système cardiovasculaire

Fares Gouzi, Aurélien Philippe, Léo Blervaque, Sven Günther, Anne Virsolvy, et al.. Plasma ratio of angiopoietin-2 to angiopoietin-1 is a biomarker of vascular impairment in chronic obstructive pulmonary disease patients. Angiogenesis, 2022, 25 (3), pp.275-277. ⟨10.1007/s10456-021-09826-1⟩. ⟨hal-03523131⟩