Intussusceptive angiogenesis in Covid-19: hypothesis on the significance and focus on the possible role of FGF2
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SHORT COMMUNICATION
Intussusceptive angiogenesis in Covid-19: hypothesis on the significance and focus on the possible role of FGF2 Simone Meini1 · Tommaso Giani2 · Carlo Tascini3 Received: 19 July 2020 / Revised: 1 September 2020 / Accepted: 7 September 2020 © Springer Nature B.V. 2020
Abstract The interest on the role of angiogenesis in the pathogenesis and progression of human interstitial lung diseases is growing, with conventional sprouting (SA) and non-sprouting intussusceptive angiogenesis (IA) being differently represented in specific pulmonary injury patterns. The role of viruses as key regulators of angiogenesis is known for several years. A significantly enhanced amount of new vessel growth, through a mechanism of IA, has been reported in lungs of patients who died from Covid-19; among the angiogenesis-related genes, fibroblast growth factor 2 (FGF2) was found to be upregulated. These findings are intriguing. FGF2 plays a role in some viral infections: the upregulation is involved in the MERS-CoV-induced strong apoptotic response crucial for its highly lytic replication cycle in lung cells, whereas FGF2 is protective against the acute lung injury induced by H1N1 influenza virus, improving the lung wet-to-dry weight ratio. FGF2 plays a role also in regulating IA, acting on pericytes (crucial for the formation of intraluminal pillars), and endothelium, and FGF2-induced angiogenesis may be promoted by inflammation and hypoxia. IA is a faster and probably more efficient process than SA, able to modulate vascular remodeling through pruning of redundant or inefficient blood vessels. We can speculate that IA might have the function of restoring a functional vascular plexus consequently to extensive endothelialitis and alveolar capillary micro-thrombosis observed in Covid-19. Anti-Vascular endothelial growth factor (anti-VEGF) strategies are currently investigated for treatment of severe and critically ill Covid-19 patients, but also FGF2, and its expression and/or signaling, might represent a promising target. Keywords Angiogenesis · Intussusceptive · FGF2 · VEGF · Covid-19 · Virus
Introduction The interest on the role of angiogenesis in the pathogenesis and progression of human interstitial lung diseases is growing, with conventional sprouting (SA) and non-sprouting intussusceptive angiogenesis (IA) being differently * Simone Meini [email protected] Tommaso Giani [email protected] Carlo Tascini [email protected] 1
Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy
2
Microbiology and Virology Unit, Careggi Hospital, University of Florence, Florence, Italy
3
Infectious Diseases Clinic, Santa Maria Misericordia Hospital, University of Udine, Udine, Italy
represented in specific pulmonary injury patterns [1]. It has been hypothesized that microvascular alterations represent one of the first steps in the pathogenesis of idiopathic pulmonary fibrosis [1, 2], and morphogenetic phenomena of plexiform vasculopathy with pronounced IA have been described also in chr
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