The role of mitochondrial fission in cardiovascular health and disease

Quiles, Justin M.; Gustafsson, Åsa B.

doi:10.1038/s41569-022-00703-y

Cited by 104 publications

(94 citation statements)

References 171 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drp1, a member of the dynamin family of GTP-binding proteins, is the primary mediator of mitochondrial fission. 29,30 Drp1 needs to be recruited to the mitochondrial surface by mitochondrial outer membrane-anchored adaptor proteins to execute its function, and Drp1 has been shown not to require Fis1 to induce mitochondrial fission in mammalian cells as opposed to the role of Fis1 in yeast. 31 Furthermore, a recent study has shown that redundancy exists among Drp1 adaptor proteins.…”

Section: Discussionmentioning

confidence: 99%

Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension

Xing

et al. 2022

Hypertension

View full text Add to dashboard Cite

BACKGROUND: Regular exercise has been recommended clinically for all individuals to protect against hypertension but the underlying mechanisms are not fully elucidated. We recently found a significant mitochondrial fragmentation in the vascular endothelium of hypertensive human subjects. In this study, we investigated whether exercise could restore endothelial mitochondrial dynamics and thus improve vascular function in hypertension. METHODS: Vascular endothelial mitochondrial morphological alterations were examined in patients with hypertension and hypertensive animal models. Furthermore, swimming exercise-induced endothelial mitochondrial dynamics and vascular function changes were investigated in spontaneously hypertensive rats (SHRs). RESULTS: Mitochondrial fragmentation with an elevated mitochondrial fission mediator Drp1 (dynamin-related protein-1) was observed in the mesenteric artery endothelium from hypertensive patients. A similar mitochondrial fragmentation with increased Drp1 expression were exhibited in the aortic endothelium of angiotensin II-induced hypertensive mice and SHRs. Interestingly, swimming exercise significantly reduced vascular Drp1 expression and alleviated endothelial mitochondrial fragmentation, thus improving blood pressure in SHRs. In cultured endothelial cells, angiotensin II exposure induced Drp1 upregulation, mitochondrial fragmentation and dysfunction, and reduced nitric oxide production, which was blunted by Drp1 genetic reduction or its inhibitor Mdivi-1. Mdivi-1 administration also ameliorated endothelial mitochondrial fragmentation, vascular dysfunction and blood pressure elevation in SHRs while swimming exercise plus Mdivi-1 treatment provided no additional benefits, suggesting that Drp1 inhibition may partially contribute to swimming exercise-conferred anti-hypertensive effects. CONCLUSIONS: These findings suggest that swimming exercise alleviates endothelial mitochondrial fragmentation via inhibiting Drp1, which may contribute to exercise-induced improvement of vascular function and blood pressure in hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension

Xing

et al. 2022

Hypertension

View full text Add to dashboard Cite

show abstract

“…Although our data suggest that ARB has anti-apoptosis effects, we were not able to determine the specific mechanisms responsible for these effects (that is, AT 1 R, PPAR-γ agonism, both, or other unknown mechanisms). Recent work has highlighted the important role of mitochondrial fusion/fission dynamics in mitochondrial homeostasis, which contributes to cardiovascular health and disease [ 34 , 35 ]. However, the current study focused on mitochondria-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Receptor Blocker Irbesartan Enhanced SIRT1 longevity Signaling Replaces the Mitochondrial Biogenetic Survival Pathway to Attenuate Hypertension-Induced Heart Apoptosis

Pai

Wong

Cui

et al. 2022

JCDD

View full text Add to dashboard Cite

Background: The present study investigated whether angiotensin II type 1 receptor blocker irbesartan (ARB) and partial agonist of PPAR-γ prevents heart apoptosis by suppressing cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis in the hearts of hypertensive rat model. Methods: Cardiac function using echocardiography, H&E staining, TUNEL assay, and Western blotting were measured in the excised hearts from three groups, i.e., an untreated hypertensive group (SHR), an ARB-treated hypertensive group (50 mg/kg/day, S.C., SHR-ARB), and untreated normotensive Wistar-Kyoto rats (WKY). Results: Fas Ligand, Fas death receptors, FADD, active caspase-8, active caspase-3 (Fas/FasL-mediated apoptotic pathway), as well as Bax, cytochrome c, active caspase-9 and -3 (mitochondria-mediated apoptotic pathway), IGF-II, and p-JNK were decreased in SHR-ARB group when compared with the SHR group. SIRT1, PGC-1α, Bcl2, and Bcl-xL (SIRT1/PGC-1α pro-survival pathway) were increased in the SHR-ARB group when compared with the SHR group. Conclusions: Our findings suggested that the ARB might prevent cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis pathway in the hypertensive model associated with IGF-II, p-JNK deactivation, and SIRT1/PGC-1α pro-survival pathway upregulation. ARB prevents hypertension-enhanced cardiac apoptosis via enhancing SIRT1 longevity signaling and enhances the mitochondrial biogenetic survival pathway.

show abstract

“…Of note, mitochondrial injury has been identified as the common pathological change in both kidney and heart in the state of CKD ( Shi et al, 2022 ). Recent studies have reported that modulating mitophagy may reverse the above pathological changes in the injured kidney and heart through eliminating damaged mitochondria and maintaining mitochondrial homeostasis ( Quiles and Gustafsson, 2022 ), hinting that mitophagy might link these pathological changes between the heart and kidney.…”

Section: Mitophagy In Cardiorenal Syndrome Typementioning

confidence: 99%

The molecular mechanisms and intervention strategies of mitophagy in cardiorenal syndrome

Yao

Liu²,

Sun³

et al. 2022

Front. Physiol.

View full text Add to dashboard Cite

Cardiorenal syndrome (CRS) is defined as a disorder of the heart and kidney, in which acute or chronic injury of one organ may lead to acute or chronic dysfunction of the other. It is characterized by high morbidity and mortality, resulting in high economic costs and social burdens. However, there is currently no effective drug-based treatment. Emerging evidence implicates the involvement of mitophagy in the progression of CRS, including cardiovascular disease (CVD) and chronic kidney disease (CKD). In this review, we summarized the crucial roles and molecular mechanisms of mitophagy in the pathophysiology of CRS. It has been reported that mitophagy impairment contributes to a vicious loop between CKD and CVD, which ultimately accelerates the progression of CRS. Further, recent studies revealed that targeting mitophagy may serve as a promising therapeutic approach for CRS, including clinical drugs, stem cells and small molecule agents. Therefore, studies focusing on mitophagy may benefit for expanding innovative basic research, clinical trials, and therapeutic strategies for CRS.

show abstract

The role of mitochondrial fission in cardiovascular health and disease

Cited by 104 publications

References 171 publications

Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension

Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension

Angiotensin II Receptor Blocker Irbesartan Enhanced SIRT1 longevity Signaling Replaces the Mitochondrial Biogenetic Survival Pathway to Attenuate Hypertension-Induced Heart Apoptosis

The molecular mechanisms and intervention strategies of mitophagy in cardiorenal syndrome

Contact Info

Product

Resources

About