Metformin as possible therapy of pulmonary arterio venous malformation in HHT patients

Abstract Hereditary hemorrhagic telangiectasia(HHT) or Rendu–Osler–Weber diseaseis an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations. Pulmonary arteriovenous malformationsmay either rupture or be responsible for a right-to- left shuntingleading to paradoxical embolismcausing stroke or cerebral abscess. Metforminmay harbor a pleiotropicaction, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress. An animal model could be experimented to show its effects on PAVM formation. Metformincould also be tested in human individuals, particularly in patients presenting a diffuse HHT type with tiny PAVM. Metforminmay be indicated as a prophylactic or curative therapy in HHT patients presenting with initial lung involvement. Metforminmay be proposed to prevent from pulmonary arteriovenous malformationdevelopment and subsequent related complications.