AMPK: Potential Therapeutic Target for Vascular Calcification

Lü, Yi; Yuan, Tan; Min, Xinjia; Yuan, Zhen; Cai, Zhejun

doi:10.3389/fcvm.2021.670222

Cited by 18 publications

(13 citation statements)

References 108 publications

(135 reference statements)

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“…In particular, cGMP-PKG is tightly correlated with diabetes vascular dysfunction and cardiomyocyte autophagy [ 39 – 41 ]. A reduction in autophagy leads to cardiac dysfunction, including cardiovascular calcification [ 42 , 43 ]. This evidence highlights the important relationship between the cGMP-PKG signalling pathway and VSMC autophagy.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

Cao

Chen

et al. 2022

J Transl Med

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Background The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear. Methods Wild-type (WT) and miR-32−/− mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32−/− mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy. Results We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32−/− mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32−/− mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells. Conclusions These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

Cao

Chen

et al. 2022

J Transl Med

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“…During the regulation of vascular smooth muscle cell differentiation, AMPK also attenuates ER stress and DRP1-mediated mitochondrial fission. 5…”

Section: Significance Of Ampk As a Potential Therapeutic Target For D...mentioning

confidence: 99%

Role of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases

Shukal

Malaviya

Sharma³

2022

Hum Exp Toxicol

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Background AMP-activated protein kinase (AMPK) plays a precise role as a master regulator of cellular energy homeostasis. AMPK is activated in response to the signalling cues that exhaust cellular ATP levels such as hypoxia, ischaemia, glucose depletion and heat shock. As a central regulator of both lipid and glucose metabolism, AMPK is considered to be a potential therapeutic target for the treatment of various diseases, including eye disorders. Objective To review all the shreds of evidence concerning the role of the AMPK signalling pathway in the pathogenesis of ocular diseases. Method Scientific data search and review of available information evaluating the influence of AMPK signalling on ocular diseases. Results Review highlights the significance of AMPK signalling in the aetiopathogenesis of ocular diseases, including cataract, glaucoma, diabetic retinopathy, retinoblastoma, age-related macular degeneration, corneal diseases, etc. The review also provides the information on the AMPK-associated pathways with reference to ocular disease, which includes mitochondrial biogenesis, autophagy and regulation of inflammatory response. Conclusion The study concludes the role of AMPK in ocular diseases. There is growing interest in the therapeutic utilization of the AMPK pathway for ocular disease treatment. Furthermore, inhibition of AMPK signalling might represent more pertinent strategy than AMPK activation for ocular disease treatment. Such information will guide the development of more effective AMPK modulators for ocular diseases. [Formula: see text]

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“…Накопичення ROS пов'язане зі збільшенням експресії RUNX2, що, у свою чергу, може призвести до розвитку остеоцитарного фенотипу VSMC. Передбачається, що дієти з високим вмістом антиоксидантів, таких як ресвератрол, можуть чинити захисну дію на судинну кальцифікацію [42]. Проте на сьогодні досліджень щодо вивчення ефективності антиоксидантів у запобіганні кальцифікації судин не проводилося.…”

Section: вплив окиснювального стресу та мітохондріальної дисфункції н...unclassified

Arterial stiffness, vascular calcification and osteoporosis — common mechanisms of interaction (literature review)

Nishkumay

Mostbauer

Alekseenko

et al. 2022

PJS

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Introduction. The problem of cardiovascular morbidity and mortality remains an urgent issue of modern medicine, and arterial stiffness is its independent predictor. Lively discussions about the correct approach to the prevention and treatment of comorbid conditions – increased vascular stiffness as an influential factor of the cardiovascular events and decreased bone mineral density (osteoporosis), primarily arise against the background of the need and safety of calcium and vitamin D supplements. The purpose was to search for literature data as for possible common pathogenetic links in the progression of arterial stiffness and the development of osteoporosis in order to assess the safety of the use of drugs to prevent osteoporotic fractures. Results. Analysis of literature sourses had showed that possible osteogenic factors affecting arterial stiffness may be: secondary hyperparathyroidism, disbalance of the RANK/RANKL/OPG system, inhibition of vitamin K-dependent matrix proteins (Gla-protein), osteopontin, etc. Conclusions. Today, there are many hypotheses confirming the possible influence of osteogenic factors on vascular stiffness and arterial calcification. Therefore, the search for sensitive markers and the development of screening protocols for the patients with risk factors for both osteoporosis and vascular changes are extremely relevant. A special issue is the possibility of using monotherapy for these comorbid pathologies, which can safely and efficiently influence the prevention of complications – both low-energy osteoporotic fractures and cardiovascular catastrophes. This will be the focus of our further research.

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AMPK: Potential Therapeutic Target for Vascular Calcification

Cited by 18 publications

References 108 publications

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy

Role of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases

Arterial stiffness, vascular calcification and osteoporosis — common mechanisms of interaction (literature review)

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