Long-Term Strenuous Exercise Promotes Vascular Injury by Selectively Damaging the Tunica Media: Experimental Evidence

Cira Rubies; Montserrat Batlle; Maria Sanz-de la Garza; Ana-Paula Dantas; Ignasi Jorba; Guerau Fernandez; Gemma Sangüesa; Marc Abuli; Josep Brugada; Marta Sitges; Daniel Navajas; Lluís Mont; Eduard Guasch

doi:10.1016/j.jacbts.2022.02.017

Long-Term Strenuous Exercise Promotes Vascular Injury by Selectively Damaging the Tunica Media: Experimental Evidence

JACC Basic Transl Sci. 2022 Jul 13;7(7):681-693. doi: 10.1016/j.jacbts.2022.02.017. eCollection 2022 Jul.

Authors

Cira Rubies¹, Montserrat Batlle^{1

2}, Maria Sanz-de la Garza³, Ana-Paula Dantas¹, Ignasi Jorba^{4

5

6}, Guerau Fernandez⁷, Gemma Sangüesa^{1

2}, Marc Abuli³, Josep Brugada^{1

2

3}, Marta Sitges^{1

2

3}, Daniel Navajas^{5

6}, Lluís Mont^{1

2

3}, Eduard Guasch^{1

2

3}

Affiliations

¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
² Centro de Investigación Biomédica en Red - Cardiovascular (CIBERCV), Madrid, Spain.
³ Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Catalonia, Spain.
⁴ Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain.
⁵ School of Medicine and Health Sciences, University of Barcelona, Catalonia, Spain.
⁶ Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), Madrid, Spain.
⁷ Bioinformatics Unit, Genetics and Molecular Medicine Service, Hospital Sant Joan de Déu, Esplugues Del Llobregat, Spain.

Abstract

Moderate exercise has well-founded benefits in cardiovascular health. However, increasing, yet controversial, evidence suggests that extremely trained athletes may not be protected from cardiovascular events as much as moderately trained individuals. In our rodent model, intensive but not moderate training promoted aorta and carotid stiffening and elastic lamina ruptures, tunica media thickening of intramyocardial arteries, and an imbalance between vasoconstrictor and relaxation agents. An up-regulation of angiotensin-converter enzyme, miR-212, miR-132, and miR-146b might account for this deleterious remodeling. Most changes remained after a 4-week detraining. In conclusion, our results suggest that intensive training blunts the benefits of moderate exercise.

Keywords: CACS, coronary artery calcium score; CAD, coronary artery disease; CV, cardiovascular; MMP9, matrix metalloproteinase 9; NO, nitric oxide; Phe, phenylephrine; VSMC, vascular smooth muscle cell; atherosclerosis; coronary artery disease; endurance exercise; extreme sport; vascular stiffening.