Harnessing the protective role of OPA1 in diabetic cardiomyopathy

Patten, David A.; Harper, Mary‐Ellen; Boardman, Neoma T.

doi:10.1111/apha.13466

Cited by 3 publications

(3 citation statements)

References 11 publications

(28 reference statements)

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“…FIS1 overexpression was expected after renal insult, as mentioned by some reports [ 65 ], but FIS was unaltered in our model. Moreover, both OPA1 and Mfn2 were reported to be decreased regarding cardiovascular disease [ 55 , 66 , 67 , 68 , 69 ], but in our study, both biomarkers were not altered in the nontreated vitamin C groups. Drp1 overexpression was also documented as a mediator of fragmentation in heart diseases and CRS [ 63 , 70 , 71 , 72 ].…”

Section: Discussioncontrasting

confidence: 73%

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C

Neres-Santos

Junho

Panico

et al. 2021

Cells

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Cardiorenal syndrome (CRS) is a pathological link between the kidneys and heart, in which an insult in a kidney or heart leads the other organ to incur damage. CRS is classified into five subtypes, and type 3 (CRS3) is characterized by acute kidney injury as a precursor to subsequent cardiovascular changes. Mitochondrial dysfunction and oxidative and nitrosative stress have been reported in the pathophysiology of CRS3. It is known that vitamin C, an antioxidant, has proven protective capacity for cardiac, renal, and vascular endothelial tissues. Therefore, the present study aimed to assess whether vitamin C provides protection to heart and the kidneys in an in vivo CRS3 model. The unilateral renal ischemia and reperfusion (IR) protocol was performed for 60 min in the left kidney of adult mice, with and without vitamin C treatment, immediately after IR or 15 days after IR. Kidneys and hearts were subsequently collected, and the following analyses were conducted: renal morphometric evaluation, serum urea and creatinine levels, high-resolution respirometry, amperometry technique for NO measurement, gene expression of mitochondrial dynamic markers, and NOS. The analyses showed that the left kidney weight was reduced, urea and creatinine levels were increased, mitochondrial oxygen consumption was reduced, NO levels were elevated, and Mfn2 expression was reduced after 15 days of IR compared to the sham group. Oxygen consumption and NO levels in the heart were also reduced. The treatment with vitamin C preserved the left kidney weight, restored renal function, reduced NO levels, decreased iNOS expression, elevated constitutive NOS isoforms, and improved oxygen consumption. In the heart, oxygen consumption and NO levels were improved after vitamin C treatment, whereas the three NOS isoforms were overexpressed. These data indicate that vitamin C provides protection to the kidneys and some beneficial effects to the heart after IR, indicating it may be a preventive approach against cardiorenal insults.

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Section: Discussioncontrasting

confidence: 73%

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C

Neres-Santos

Junho

Panico

et al. 2021

Cells

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“…Recent studies suggest that Opa1 is downregulated in various cell types and tissues under HG or diabetic conditions [ 32 , 33 , 34 , 35 , 36 ]. Cerebral vascular smooth muscle cells grown in HG medium exhibited a significant reduction in Opa1 expression and resulted in increased mitochondrial fragmentation that contributed to compromised contractility and decreased cell proliferation [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Opa1 Deficiency Promotes Development of Retinal Vascular Lesions in Diabetic Retinopathy

Kim

Votruba

Roy

2021

IJMS

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This study investigates whether reduced optic atrophy 1 (Opa1) level promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy (DR). Four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Opa1+/− mice, and diabetic Opa1+/− mice were used in this study. 16 weeks after diabetes onset, retinas were assessed for Opa1 and Bax levels by Western blot analysis, and retinal networks were examined for acellular capillaries (AC) and pericyte loss (PL). Apoptotic cells were detected in retinal capillaries using TUNEL assay, and caspase-3 activity was assessed using fluorometric analysis. Opa1 expression was significantly downregulated in retinas of diabetic and Opa1+/− mice compared with those of WT mice. Inducing diabetes further decreased Opa1 expression in retinas of Opa1+/− mice. Increased cytochrome c release concomitant with increased level of pro-apoptotic Bax and elevated caspase-3 activity were observed in retinas of diabetic and Opa1+/− mice; the number of TUNEL-positive cells and AC/PL was also significantly increased. An additional decrease in the Opa1 level in retinas of diabetic Opa1+/− mice exacerbated the development of apoptotic cells and AC/PL compared with those of diabetic mice. Diabetes-induced Opa1 downregulation contributes, at least in part, to the development of retinal vascular lesions characteristic of DR.

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“… 20 , 21 Besides, the signaling also influences endothelial nitric oxide synthase (eNOS), triggering the bioavailable nitric oxide (NO) for proper microvascular flow and myocardial function. 20 , 22 Several epidemiological studies have reported a connection between abnormal insulin signaling and HF. 23 , 24 Insulin resistance has also been correlated with increased serum concentrations of pro-inflammatory cytokines, catecholamines, and growth hormones in HF.…”

Section: Impaired Insulin Signalingmentioning

confidence: 99%

A comprehensive review of the novel therapeutic targets for the treatment of diabetic cardiomyopathy

Dhar,

Venkadakrishnan,

Roy

et al. 2023

Therapeutic Advances in Cardiovascular Disease

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Diabetic cardiomyopathy (DCM) is characterized by structural and functional abnormalities in the myocardium affecting people with diabetes. Treatment of DCM focuses on glucose control, blood pressure management, lipid-lowering, and lifestyle changes. Due to limited therapeutic options, DCM remains a significant cause of morbidity and mortality in patients with diabetes, thus emphasizing the need to develop new therapeutic strategies. Ongoing research is aimed at understanding the underlying molecular mechanism(s) involved in the development and progression of DCM, including oxidative stress, inflammation, and metabolic dysregulation. The goal is to develope innovative pharmaceutical therapeutics, offering significant improvements in the clinical management of DCM. Some of these approaches include the effective targeting of impaired insulin signaling, cardiac stiffness, glucotoxicity, lipotoxicity, inflammation, oxidative stress, cardiac hypertrophy, and fibrosis. This review focuses on the latest developments in understanding the underlying causes of DCM and the therapeutic landscape of DCM treatment.

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Harnessing the protective role of OPA1 in diabetic cardiomyopathy

Cited by 3 publications

References 11 publications

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C

Opa1 Deficiency Promotes Development of Retinal Vascular Lesions in Diabetic Retinopathy

A comprehensive review of the novel therapeutic targets for the treatment of diabetic cardiomyopathy

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