The role of mitochondria-derived peptides in cardiovascular disease: Recent updates

Yang, Yingxi; Gao, Huijuan; Zhou, Huan; Liu, Qi; Qi, Zhongwen; Zhang, Ying; Zhang, Junping

doi:10.1016/j.biopha.2019.109075

Cited by 58 publications

(50 citation statements)

References 96 publications

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“…Recently, it has been found that MDPs have important effects on the development of CVD. 42 MDPs are linked with CV risk factors. They exert a cardioprotective effect by interfering with various risk factors, such as aging, insulin resistance, hyperlipidemia, and atherosclerosis.…”

Section: Mitochondria-derived Peptides (Mdps)mentioning

confidence: 99%

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Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

Manolis¹,

Manolis

et al. 2020

Medicinal Research Reviews

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Mitochondria provide energy to the cell during aerobic respiration by supplying ~95% of the adenosine triphosphate (ATP) molecules via oxidative phosphorylation. These organelles have various other functions, all carried out by numerous proteins, with the majority of them being encoded by nuclear DNA (nDNA). Mitochondria occupy ~1/3 of the volume of myocardial cells in adults, and function at levels of high‐efficiency to promptly meet the energy requirements of the myocardial contractile units. Mitochondria have their own DNA (mtDNA), which contains 37 genes and is maternally inherited. Over the last several years, a variety of functions of these organelles have been discovered and this has led to a growing interest in their involvement in various diseases, including cardiovascular (CV) diseases. Mitochondrial dysfunction relates to the status where mitochondria cannot meet the demands of a cell for ATP and there is an enhanced formation of reactive‐oxygen species. This dysfunction may occur as a result of mtDNA and/or nDNA mutations, but also as a response to aging and various disease and environmental stresses, leading to the development of cardiomyopathies and other CV diseases. Designing mitochondria‐targeted therapeutic strategies aiming to maintain or restore mitochondrial function has been a great challenge as a result of variable responses according to the etiology of the disorder. There have been several preclinical data on such therapies, but clinical studies are scarce. A major challenge relates to the techniques needed to eclectically deliver the therapeutic agents to cardiac tissues and to damaged mitochondria for successful clinical outcomes. All these issues and progress made over the last several years are herein reviewed.

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Section: Mitochondria-derived Peptides (Mdps)mentioning

confidence: 99%

“…However, there is still a lot to be done until one could use MDPs for clinical therapeutic purposes. 42…”

Section: Mitochondria-derived Peptides (Mdps)mentioning

confidence: 99%

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

Manolis¹,

Manolis

et al. 2020

Medicinal Research Reviews

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“…The overaccumulation of Ca 2+ in mitochondria causes the transient depolarization of the IMM [47], leading to the opening of mPTPs, which are voltage-dependent, high-conductance channels [48]. The uncontrolled opening of mPTPs leads to MMP collapse, and several pro-apoptotic proteins, such as cytochrome c and apoptosis inducing factor (AIF), are released into the cytosol from the intermembrane space through mPTPs, where they modulate the final steps of the apoptotic cascade [49,50].…”

Section: Discussionmentioning

confidence: 99%

Sedum takesimense Protects PC12 Cells against Corticosterone-Induced Neurotoxicity by Inhibiting Neural Apoptosis

Yun

Jeong

2020

Nutrients

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Neuronal cell death induced by chronic stress in the central nervous system is a cause of neurological dysfunction. We investigated the neuroprotective potential of a water extract of S. takesimense (WEST) against corticosterone-induced apoptosis in PC12 cells and the possible underlying mechanisms. Cells were pretreated with 50 µg/mL of WEST to evaluate its neuroprotective effect based on endoplasmic reticulum (ER) stress inhibition and mitochondrial function improvement. Pretreatment with WEST prevented corticosterone-induced injury in PC12 cells, resulting in increased cell survival, decreased lactate dehydrogenase (LDH) release, and potent apoptosis inhibition by a reduction in apoptotic nuclei demonstrated by Hoechst 33,342 and propidium iodide (PI) double staining, and TUNEL staining. WEST strongly attenuated calcium (Ca2+) elevation, inducing the closure of mitochondrial permeability transition pores (mPTPs), which were opened by corticosterone. It also stabilized mitochondrial membrane potential (MMP) loss and inhibited the corticosterone-induced decrease in adenosine triphosphate (ATP) levels. Furthermore, the increased reactive oxygen species (ROS) production induced by corticosterone was prevented in PC12 cells treated with WEST. WEST also downregulated the expression of glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), the pro-apoptotic protein Bcl-2-associated X (Bax), cytochrome c, cysteine-aspartic protease (caspase)-9, and caspase-3, and upregulated the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Thus, WEST exerts a neuroprotective effect by inhibiting the apoptosis pathway in ER stress and the mitochondrial dysfunction induced by corticosterone. These results demonstrate that WEST reduces neuronal damage from the neurotoxicity caused by chronic stress.

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“…Given the fact that the influential effects of physical exercise and Ang II type 1 (AT 1 ) receptor antagonists on GDF15 and FGF21 [179, 180], whether GDF15 and FGF21 have the potential to evaluate the prognosis of patients with HF treated by angiotensin receptor-neprilysin inhibitor (ARNI) has not yet been determined. MDPs [105] and UPR mt [157] are typical examples of mitochondrial reverse regulation of nuclear metabolic gene expression, providing a novel therapeutic approach. As previously mentioned, FGF21 [90], MOTS-c [103], and irisin [181] are regulated by AMPK; ATFs activates UPR mt [10] and FGF21; ERK1/2 is activated by HNG, SHLPs [104], and FGF21 [90].…”

Section: Discussionmentioning

confidence: 99%

“…MOTS-c and SHLPs further complement the role of MDPs in cell metabolism [103, 104]. Recently, the metabolic protection mechanism of MDPs in CVDs has been gradually recognized [105].…”

Section: Protective Factors For Hfmentioning

confidence: 99%

Metabolic remodeling induced by mitokines in heart failure

Duan

Chen

et al. 2019

Aging

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The prevalence rates of heart failure (HF) are greater than 10% in individuals aged >75 years, indicating an intrinsic link between aging and HF. It has been recognized that mitochondrial dysfunction contributes to the pathology of HF. Mitokines are a type of cytokines, peptides, or signaling pathways produced or activated by the nucleus or the mitochondria through cell non-autonomous responses during cellular stress. In addition to promoting the communication between the mitochondria and the nucleus, mitokines also exert a systemic regulatory effect by circulating to distant tissues. It is noteworthy that increasing evidence has demonstrated that mitokines are capable of reducing the metabolic-related HF risk factors and are associated with HF severity. Consequently, mitokines might represent a potential therapy target for HF.

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The role of mitochondria-derived peptides in cardiovascular disease: Recent updates

Cited by 58 publications

References 96 publications

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

Sedum takesimense Protects PC12 Cells against Corticosterone-Induced Neurotoxicity by Inhibiting Neural Apoptosis

Metabolic remodeling induced by mitokines in heart failure

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