Role of Oxidative Stress and Autophagy in Thoracic Aortic Aneurysms

Francesco G Irace; Vittoria Cammisotto; Valentina Valenti; Maurizio Forte; Leonardo Schirone; Simona Bartimoccia; Alessandra Iaccarino; Mariangela Peruzzi; Sonia Schiavon; Andrea Morelli; Antonino G M Marullo; Fabio Miraldi; Cristina Nocella; Ruggero De Paulis; Umberto Benedetto; Ernesto Greco; Giuseppe Biondi-Zoccai; Sebastiano Sciarretta; Roberto Carnevale; Giacomo Frati

doi:10.1016/j.jacbts.2021.08.002

Role of Oxidative Stress and Autophagy in Thoracic Aortic Aneurysms

JACC Basic Transl Sci. 2021 Oct 25;6(9-10):719-730. doi: 10.1016/j.jacbts.2021.08.002. eCollection 2021 Sep-Oct.

Authors

Francesco G Irace^{1

2}, Vittoria Cammisotto^{2

3}, Valentina Valenti⁴, Maurizio Forte⁵, Leonardo Schirone⁴, Simona Bartimoccia⁴, Alessandra Iaccarino⁶, Mariangela Peruzzi^{4

7}, Sonia Schiavon⁴, Andrea Morelli³, Antonino G M Marullo⁴, Fabio Miraldi³, Cristina Nocella³, Ruggero De Paulis¹, Umberto Benedetto⁸, Ernesto Greco³, Giuseppe Biondi-Zoccai^{4

7}, Sebastiano Sciarretta^{4

5}, Roberto Carnevale^{4

7}, Giacomo Frati^{4

5}

Affiliations

¹ Department of Cardiac Surgery, European Hospital, Rome, Italy.
² Department of General and Specialized Surgery "Paride Stefanini," Sapienza University of Rome, Rome, Italy.
³ Department of Clinical Internal, Anesthesiological, and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
⁴ Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
⁵ IRCCS Neuromed, Pozzilli (IS), Italy.
⁶ Department of Cardiothoracic Surgery, Humanitas Clinical and Research Centre, IRCCS, Milan, Italy.
⁷ Mediterranea Cardiocentro, Naples, Italy.
⁸ Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.

Abstract

Thoracic aortic aneurysms (TAA) pathogenesis and progression include many mechanisms. The authors investigated the role of autophagy, oxidative stress, and endothelial dysfunction in 36 TAA patients and 23 control patients. Univariable and multivariable analyses were performed. TAA patients displayed higher oxidative stress and endothelial dysfunction then control patients. Autophagy in the TAA group was reduced. The association of oxidative stress and autophagy with aortic disease supports the role of these processes in TAA. The authors demonstrate a putative role of Nox2 and autophagy dysregulation in human TAA. These findings could pinpoint novel treatment targets to prevent or limit TAA progression.

Keywords: ATG5, autophagy protein 5; HBA, hydrogen peroxide break-down activity; HRP, horseradish peroxidase; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; PAGE, polyacrylamide gel electrophoresis; ROS, reactive oxygen species; SDS, sodium dodecyl sulfate; TAA, thoracic aortic aneurysms; VSMC, vascular smooth muscle cell; autophagy; endothelial dysfunction; oxidative stress; sNox2-dp, soluble Nox2-derived peptide; thoracic aortic aneurysm.