An Intervention Target for Myocardial Fibrosis: Autophagy

Myocardial fibrosis (MF) is the result of metabolic imbalance of collagen synthesis and metabolism, which is widespread in various cardiovascular diseases. Autophagy is a lysosomal degradation pathway which is highly conserved. In recent years, research on autophagy has been increasing and the researchers have also become cumulatively aware of the specified association between autophagy and MF. This review highlights the role of autophagy in MF and the potential effects through the administration of medicine.

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Protein crowding mediates membrane remodeling in upstream ESCRT-induced formation of intraluminal vesicles

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2014228117 ◽

2020 ◽

Vol 117 (46) ◽

pp. 28614-28624

Author(s):

Susanne Liese ◽

Eva Maria Wenzel ◽

Ingrid Kjos ◽

Rossana Rojas Molina ◽

Sebastian W. Schultz ◽

...

Keyword(s):

Degradation Pathway ◽

Bending Rigidity ◽

Lysosomal Degradation ◽

Endosomal Sorting ◽

Electron Microscopy Analysis ◽

Steep Decline ◽

Microscopy Analysis ◽

Protein Crowding ◽

Membrane Shape

As part of the lysosomal degradation pathway, the endosomal sorting complexes required for transport (ESCRT-0 to -III/VPS4) sequester receptors at the endosome and simultaneously deform the membrane to generate intraluminal vesicles (ILVs). Whereas ESCRT-III/VPS4 have an established function in ILV formation, the role of upstream ESCRTs (0 to II) in membrane shape remodeling is not understood. Combining experimental measurements and electron microscopy analysis of ESCRT-III–depleted cells with a mathematical model, we show that upstream ESCRT-induced alteration of the Gaussian bending rigidity and their crowding in concert with the transmembrane cargo on the membrane induce membrane deformation and facilitate ILV formation: Upstream ESCRT-driven budding does not require ATP consumption as only a small energy barrier needs to be overcome. Our model predicts that ESCRTs do not become part of the ILV, but localize with a high density at the membrane neck, where the steep decline in the Gaussian curvature likely triggers ESCRT-III/VPS4 assembly to enable neck constriction and scission.

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The Impact of Autophagy on The Differentiation of Immune Cells

International Journal of Diabetes & Metabolic Disorders ◽

10.33140/ijdmd.06.02.02 ◽

2021 ◽

Vol 6 (2) ◽

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Degradation Pathway ◽

Lysosomal Degradation ◽

Specific Mechanism ◽

Multiple Functions ◽

Selective Degradation ◽

Proliferation And Differentiation ◽

The Impact

Autophagy, as a conservative lysosomal degradation pathway, has been well studied for its multiple functions in the immune system. Autophagy has been gradually explored for the regulation of immune cell differentiation. In order to explore the specific mechanism, it is necessary to summarize the role of autophagy in the proliferation and differentiation of immune cells. It is summarized the effects of autophagy in some researches on the function and differentiation of immune cells by introducing the function of autophagy selective degradation. In this review, we discuss the effect of autophagy in the differentiation of immune cells.

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RAB18 impacts autophagy via lipid droplet-derived lipid transfer and is rescued by ATG9A

10.1101/421677 ◽

2018 ◽

Cited By ~ 1

Author(s):

Fazilet Bekbulat ◽

Daniel Schmitt ◽

Anne Feldmann ◽

Heike Huesmann ◽

Stefan Eimer ◽

...

Keyword(s):

Lipid Droplet ◽

Transmembrane Protein ◽

Degradation Pathway ◽

Rab Gtpase ◽

Lipid Transfer ◽

Lysosomal Degradation ◽

Autophagosome Formation ◽

Autophagic Activity ◽

Rescue Mechanism

AbstractAutophagy is a lysosomal degradation pathway that mediates protein and organelle turnover and maintains cellular homeostasis. Autophagosomes transport cargo to lysosomes and their formation is dependent on an appropriate lipid supply. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet (LD) metabolism, resulting in an impaired fatty acid mobilization. The reduced LD-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network, which include increased ATG2B expression and ATG12-ATG5 conjugate formation as well as enhanced ATG2B and ATG9A phosphorylation. Phosphorylation of ATG9A directs this transmembrane protein to the site of autophagosome formation and this particular modification is sufficient to rescue autophagic activity under basal conditions in the absence of RAB18. However, it is incapable of enabling an increased autophagy under inductive conditions. Thus, we illustrate the role of RAB18 in connecting LDs and autophagy, further emphasize the importance of LD-derived lipids for the degradative pathway, and characterize an ATG9A phosphorylation-dependent autophagy rescue mechanism as an adaptive response that maintains autophagy under conditions of reduced LD-derived lipid availability.

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MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Cellular Physiology and Biochemistry ◽

10.1159/000445568 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2103-2122 ◽

Cited By ~ 20

Author(s):

Peng Deng ◽

Ling Chen ◽

Zheng Liu ◽

Ping Ye ◽

Sihua Wang ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiac Function ◽

Myocardial Fibrosis ◽

Cardiac Fibrosis ◽

Cardiac Fibroblasts ◽

Pressure Overload ◽

Heart Cell ◽

Factor C

Background/Aims: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. Methods: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. Results: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. Conclusion: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload-induced cardiac fibrosis by regulating c-Myb.

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The Role of sST-2 in Predicting Cardiovascular Diseases

Kardiologiia vid nauky do praktyky ◽

10.30702/card:sp.2019.05.036/0223853 ◽

2019 ◽

pp. 38-53

Author(s):

Ja. Hilova ◽

M. Kopytsya ◽

J. Rodionova

Keyword(s):

Cardiovascular Diseases

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Role of intestinal microbiota in cardiovascular diseases

Practical medicine ◽

10.32000/2072-1757-2020-1-54-59 ◽

2020 ◽

Vol 18 (1) ◽

pp. 54-59

Author(s):

R. A. FAYZULLINA ◽

◽

K. A. SAFINA ◽

Keyword(s):

Cardiovascular Diseases ◽

Intestinal Microbiota

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The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

Protein and Peptide Letters ◽

10.2174/0929866527666200127115059 ◽

2020 ◽

Vol 27 (6) ◽

pp. 520-528 ◽

Cited By ~ 2

Author(s):

Izabela Guimarães Barbosa ◽

Giulia Campos Ferreira ◽

Diomildo Ferreira Andrade Júnior ◽

Cássio Rocha Januário ◽

André Rolim Belisário ◽

...

Keyword(s):

Systematic Review ◽

Bipolar Disorder ◽

Cardiovascular Diseases ◽

Renin Angiotensin System ◽

Plasma Renin ◽

Angiotensin Receptors ◽

Angiotensin System ◽

Renin Angiotensin ◽

Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

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