dc.contributor.advisor | García Rivas, Gerardo de Jesus | |
dc.contributor.author | Bernal Ramírez, Judith | |
dc.date.accessioned | 2022-03-03T19:55:09Z | |
dc.date.available | 2022-03-03T19:55:09Z | |
dc.date.created | 2021 | |
dc.date.issued | 2021-06 | |
dc.identifier.citation | Bernal-Ramírez, J. (2021). The Role of Mitochondrial Hyperacetylation and Sirtuin Activity in Pulmonary Arterial Hypertension. (Tesis doctoral). Instituto Tecnológico y de Estudios Superiores de Monterrey. | es_MX |
dc.identifier.uri | https://hdl.handle.net/11285/645483 | |
dc.description | https://orcid.org/0000-0003-4731-3293 | es_MX |
dc.description.abstract | Cardiovascular diseases (CVDs) are the number one cause of death globally, causing 17.9 million deaths annually. The left ventricle (LV) has received significant attention to describe the mechanism involved in its dysfunction, unlike the right ventricle (RV). However, this has changed in the last decades. LV and RV adapt their mechanisms at the cellular and tissular level to fulfill heart function. However, the physiological differences in structure, function and molecular adaptations of both ventricles result in different responses to stressful stimuli. Unfortunately, mechanisms associated with RV dysfunction are not as widely studied as those related to LV dysfunction. Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disease characterized by an increase in pulmonary vascular pressure, leading to ventricular failure withhigh morbidity and mortality. While RV failure is the strongest predictor of mortality, there are no definitive therapies directly targeting RV dysfunction. Resveratrol (RES), a phenolic compound and a sirtuin pathway activator, is known for anti-inflammatory and cardiovascular benefits. In PAH, RES exhibits cardioprotective effects on RV; however, most literature has focused on its protective effect on lung vasculature. Using a murine model of PAH induced by monocrotaline, the effects of a daily oral dose of RES were evaluated by determining its impact on the lungs and the right and left ventricular function. Although significant differences in the pulmonary architecture were not identified, RES has a protective effect against RV dysfunction and pathological remodeling changes by delaying PAH progression. PAH significantly affects mitochondrial function in RV at the cellular level, making it prone to mitochondrial permeability transition pore (mPTP) opening, thus decreasing the mitochondrial membrane potential. The compromised cellular energetics affect cardiomyocyte function by disrupting cell relaxation. RES partially protects mitochondrial integrity by deacetylating cyclophilin-D, a critical component of the mPTP, increasing SIRT3 expression and activity, preventing mPTP opening and avoiding the impairment in excitation-contraction-energetics coupling in RV failure. These results highlight the importance of mitochondrial energetics and mPTP in PAH and the use of RES as a future potential adjunct therapy. | es_MX |
dc.format.medium | Texto | es_MX |
dc.language.iso | eng | es_MX |
dc.publisher | Instituto Tecnológico y de Estudios Superiores de Monterrey | es_MX |
dc.relation.isFormatOf | versión publicada | es_MX |
dc.rights | openAccess | es_MX |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0 | es_MX |
dc.subject.classification | MEDICINA Y CIENCIAS DE LA SALUD::CIENCIAS MÉDICAS::MEDICINA INTERNA::CARDIOLOGÍA | es_MX |
dc.subject.lcsh | Medicine | es_MX |
dc.title | The Role of Mitochondrial Hyperacetylation and Sirtuin Activity in Pulmonary Arterial Hypertension | es_MX |
dc.type | Tesis Doctorado / doctoral Thesis | es_MX |
dc.contributor.department | School of Engineering and Sciences | es_MX |
dc.contributor.committeemember | Contreras Torres, Flavio Fernando | |
dc.contributor.committeemember | Gutiérrez Uribe, Janet Alejandra | |
dc.contributor.committeemember | Zarain Herzberg, Angel Alfonso | |
dc.identifier.orcid | http://orcid.org/0000-0003-1223-7366 | es_MX |
dc.subject.keyword | Sirtuin | es_MX |
dc.subject.keyword | Mitochondrial function | es_MX |
dc.subject.keyword | Calcium signaling | es_MX |
dc.subject.keyword | Pulmonary arterial hypertension | es_MX |
dc.subject.keyword | Resveratrol | es_MX |
dc.contributor.institution | Campus Monterrey | es_MX |
dc.contributor.cataloger | tolmquevedo | es_MX |
dc.description.degree | Doctor in Biotechnology | es_MX |
dc.date.accepted | 2021-06-02 | |
dc.audience.educationlevel | Investigadores/Researchers | es_MX |
dc.identifier.scopusid | 55762832900 | es_MX |
dc.identificator | 3||32||3205||320501 | es_MX |