Dottore di ricerca

ciclo: XXXVI

supervisore: Prof. Isotta Chimenti
co-supervisore: Prof. Isotta Chimenti

Titolo della tesi: Role of OPA1 in endothelial dysfunction

Cardiovascular diseases (CVDs) are the leading cause of death in the world and one of the most important public health problems, being also among the main causes of comorbidity and disability. The role of endothelium in vascular health is well-known, and its dysfunction is associated with cardiovascular disorders. Emerging evidence demonstrated that defects of mitochondrial dynamics are associated with the onset and development of several cardiac diseases, making mitochondrial dynamics a potential therapeutic target. Optic Atrophy 1 (OPA1) regulates mitochondrial fusion and exerts cardioprotective effects. However, the role of OPA1 in endothelial cells in response to cardiovascular stress is completely unknown. This study investigated the effects of OPA1 modulation in endothelial cells undergoing treatment with common cardiovascular risk factors. Human umbilical vein endothelial cells (HUVECs) were exposed to conditions mimicking type 2 diabetes (high glucose, HG 30mM), hypercholesterolemia (oxidised LDL, ox-LDL 30μg/ml), and smoking (cigarette smoke condensate, CSC 20 μg/ml). OPA1 levels, mitochondrial network, mitochondrial activity, nitric oxide (NO) production, oxidative stress and angiogenesis were evaluated in these conditions, in the presence or the absence of OPA1 gene silencing or OPA1 overexpression. The effects of OPA1 overexpression were also evaluated on endothelial-dependent vasorelaxation in isolated arteries from mice subjected to stress ex vivo. I demonstrated that short-time exposure to cardiovascular stressors increases OPA1 levels in endothelial cells affecting mitochondrial dynamics and function. OPA1 gene silencing exacerbates stress-induced endothelial dysfunction whereas OPA1 overexpression rescues it. My results suggest that OPA1 may be considered an interesting therapeutic target for the reduction of CVDs in individuals at high risk, such as smokers, and patients with diabetes, obesity or metabolic syndrome.

Produzione scientifica

11573/1701914 - 2024 - Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells
Nesci, Salvatore; Algieri, Cristina; Tallarida, Matteo Antonio; Stanzione, Rosita; Marchi, Saverio; Pietrangelo, Donatella; Trombetti, Fabiana; D'ambrosio, Luca; Forte, Maurizio; Cotugno, Maria; Nunzi, Ilaria; Bigi, Rachele; Maiuolo, Loredana; De Nino, Antonio; Pinton, Paolo; Romeo, Giovanni; Rubattu, Speranza - 01a Articolo in rivista
rivista: EUROPEAN JOURNAL OF CELL BIOLOGY (Jena: Urban & Fischer Verlag) pp. 1-14 - issn: 0171-9335 - wos: (0) - scopus: (0)

11573/1664951 - 2023 - Natural activators of autophagy reduce oxidative stress and muscle injury biomarkers in endurance athletes. a pilot study
D’Amico, Alessandra; Fossati, Chiara; Pigozzi, Fabio; Borrione, Paolo; Peruzzi, Mariangela; Bartimoccia, Simona; Saba, Filippo; Pingitore, Annachiara; Biondi Zoccai, Giuseppe; Petramala, Luigi; De Grandis, Fabrizio; Vecchio, Daniele; D’Ambrosio, Luca; Schiavon, Sonia; Sciarra, Luigi; Nocella, Cristina; Cavarretta, Elena - 01a Articolo in rivista
rivista: NUTRIENTS (Basel, Switzerland: Molecular Diversity Preservation International (MDPI)) pp. - - issn: 2072-6643 - wos: WOS:000916140400001 (0) - scopus: 2-s2.0-85146666417 (1)

11573/1687694 - 2023 - MST1 mediates doxorubicin-induced cardiomyopathy by SIRT3 downregulation
Schirone, Leonardo; Vecchio, Daniele; Valenti, Valentina; Forte, Maurizio; Relucenti, Michela; Angelini, Annalisa; Zaglia, Tania; Schiavon, Sonia; D'ambrosio, Luca; Sarto, Gianmarco; Stanzione, Rosita; Mangione, Elisa; Miglietta, Selenia; Di Bona, Anna; Fedrigo, Marny; Ghigo, Alessandra; Versaci, Francesco; Petrozza, Vincenzo; Marchitti, Simona; Rubattu, Speranza; Volpe, Massimo; Sadoshima, Junichi; Frati, Luigi; Frati, Giacomo; Sciarretta, Sebastiano - 01a Articolo in rivista
rivista: CELLULAR AND MOLECULAR LIFE SCIENCES (Birkhaeuser Verlag AG:Viaduktstrasse 42-44, CH 4051 Basel Switzerland:011 41 61 2050707, EMAIL:, INTERNET:, Fax: 011 41 61 2050792) pp. - - issn: 1420-682X - wos: WOS:001048232700001 (3) - scopus: 2-s2.0-85168221238 (3)

11573/1686401 - 2023 - Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension. A pilot study
Tocci, Giuliano; Biondi-Zoccai, Giuseppe; Forte, Maurizio; Gallo, Giovanna; Nardoianni, Giulia; Fiori, Emiliano; D'ambrosio, Luca; Di Pietro, Riccardo; Stefanini, Giulio; Cannata, Francesco; Rocco, Erica; Simeone, Beatrice; Sarto, Gianmarco; Schirone, Leonardo; D'amico, Alessandra; Peruzzi, Mariangela; Nocella, Cristina; Volpe, Massimo; Rubattu, Speranza - 01a Articolo in rivista
rivista: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES (-Amsterdam : Elsevier -Berlin : Springer -Milano: Medikal Press.) pp. 1-7 - issn: 0939-4753 - wos: WOS:001106738500001 (1) - scopus: 2-s2.0-85168364352 (1)

11573/1615940 - 2022 - The impact of autophagy modulation on phenotype and survival of cardiac stromal cells under metabolic stress
Chimenti, Isotta; Picchio, Vittorio; Pagano, Francesca; Schirone, Leonardo; Schiavon, Sonia; D'ambrosio, Luca; Valenti, Valentina; Forte, Maurizio; Di Nonno, Flavio; Rubattu, Speranza Donatella; Peruzzi, Mariangela; Versaci, Francesco; Greco, Ernesto; Calogero, Antonella; De Falco, Elena; Frati, Giacomo; Sciarretta, Sebastiano - 01a Articolo in rivista
rivista: CELL DEATH DISCOVERY ([London]: Nature Publishing Group, 2015-) pp. - - issn: 2058-7716 - wos: WOS:000777182100004 (3) - scopus: 2-s2.0-85127502865 (4)

11573/1657265 - 2022 - Natural activators of autophagy increase maximal walking distance and reduce oxidative stress in patients with peripheral artery disease. a pilot study
Martinelli, Ombretta; Peruzzi, Mariangela; Bartimoccia, Simona; D'amico, Alessandra; Marchitti, Simona; Rubattu, Speranza; Chiariello, Giovanni Alfonso; D'ambrosio, Luca; Schiavon, Sonia; Miraldi, Fabio; Saade, Wael; D'abramo, Mizar; Pingitore, Annachiara; Loffredo, Lorenzo; Nocella, Cristina; Forte, Maurizio; Pignatelli, Pasquale - 01a Articolo in rivista
rivista: ANTIOXIDANTS (Basel: MDPI) pp. - - issn: 2076-3921 - wos: WOS:000856175700001 (1) - scopus: 2-s2.0-85138519195 (3)

11573/1649151 - 2022 - Mitochondria and doxorubicin-induced cardiomyopathy. A complex interplay
Schirone, Leonardo; D'ambrosio, Luca; Maurizio, Forte; Riccardo, Genovese; Schiavon, Sonia; Spinosa, Giulia; Giuliano, Iacovone; Valenti, Valentina; Frati, Giacomo; Sciarretta, Sebastiano - 01g Articolo di rassegna (Review)
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. - - issn: 2073-4409 - wos: WOS:000823470400001 (22) - scopus: 2-s2.0-85132260638 (28)

11573/1626865 - 2022 - An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives
Schirone, Leonardo; Forte, Maurizio; D'ambrosio, Luca; Valenti, Valentina; Vecchio, Daniele; Schiavon, Sonia; Spinosa, Giulia; Sarto, Gianmarco; Petrozza, Vincenzo; Frati, Giacomo; Sciarretta, Sebastiano - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 1165- - issn: 2073-4409 - wos: WOS:000781320500001 (20) - scopus: 2-s2.0-85127391369 (29)

11573/1628838 - 2022 - Aging-Related Decline of Autophagy in Patients with Atrial Fibrillation—A Post Hoc Analysis of the ATHERO-AF Study
Versaci, F.; Valenti, V.; Forte, M.; Cammisotto, V.; Nocella, C.; Bartimoccia, S.; Schirone, L.; Schiavon, S.; Vecchio, D.; D'ambrosio, L.; Spinosa, G.; D'amico, A.; Chimenti, I.; Violi, F.; Frati, G.; Pignatelli, P.; Sciarretta, S.; Pastori, D.; Carnevale, R. - 01a Articolo in rivista
rivista: ANTIOXIDANTS (Basel: MDPI) pp. 1-11 - issn: 2076-3921 - wos: WOS:000785560300001 (4) - scopus: 2-s2.0-85127437654 (4)

11573/1617358 - 2021 - H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets
Boccellino, M.; Galasso, G.; Ambrosio, P.; Stiuso, P.; Lama, S.; Di Zazzo, E.; Schiavon, S.; Vecchio, D.; D'ambrosio, L.; Quagliuolo, L.; Feola, A.; Frati, G.; Di Domenico, M. - 01a Articolo in rivista
rivista: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (London: Hindawi AUSTIN, USA, TX: LANDES BIOSCIENCE) pp. - - issn: 1942-0900 - wos: (0) - scopus: 2-s2.0-85117286263 (4)

11573/1565089 - 2021 - Accelerating the mdx heart histo-pathology through physical exercise
Morroni, J.; Schirone, L.; Vecchio, D.; Nicoletti, C.; D'ambrosio, L.; Valenti, V.; Sciarretta, S.; Lozanoska-Ochser, B.; Bouche, M. - 01a Articolo in rivista
rivista: LIFE (Basel: MDPI) pp. 1-13 - issn: 2075-1729 - wos: WOS:000677355100001 (4) - scopus: 2-s2.0-85111390196 (4)

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