Mechanisms contributing to cardiac remodelling

2017 ◽  
Vol 131 (18) ◽  
pp. 2319-2345 ◽  
Author(s):  
Qing-Qing Wu ◽  
Yang Xiao ◽  
Yuan Yuan ◽  
Zhen-Guo Ma ◽  
Hai-Han Liao ◽  
...  
Keyword(s):  
Cellular Responses ◽  
Cardiac Remodelling ◽  
Signalling Pathways ◽  
Neurohormonal Activation ◽  
Functional Changes ◽  
Biomechanical Stress ◽  
Cardiovascular Damage ◽  
Ischaemia Reperfusion ◽  
Clinical Heart Failure ◽  
Cellular Dysfunction

Cardiac remodelling is classified as physiological (in response to growth, exercise and pregnancy) or pathological (in response to inflammation, ischaemia, ischaemia/reperfusion (I/R) injury, biomechanical stress, excess neurohormonal activation and excess afterload). Physiological remodelling of the heart is characterized by a fine-tuned and orchestrated process of beneficial adaptations. Pathological cardiac remodelling is the process of structural and functional changes in the left ventricle (LV) in response to internal or external cardiovascular damage or influence by pathogenic risk factors, and is a precursor of clinical heart failure (HF). Pathological remodelling is associated with fibrosis, inflammation and cellular dysfunction (e.g. abnormal cardiomyocyte/non-cardiomyocyte interactions, oxidative stress, endoplasmic reticulum (ER) stress, autophagy alterations, impairment of metabolism and signalling pathways), leading to HF. This review describes the key molecular and cellular responses involved in pathological cardiac remodelling.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

scholarly journals Linking mitochondrial and chloroplast retrograde signalling in plants

2020 ◽  
Vol 375 (1801) ◽  
pp. 20190410 ◽  
Author(s):  
Yan Wang ◽  
Jennifer Selinski ◽  
Chunli Mao ◽  
Yanqiao Zhu ◽  
Oliver Berkowitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Gene ◽  
Signalling Pathways ◽  
Theme Issue ◽  
Functional Changes ◽  
Nuclear Gene Expression ◽  
Retrograde Signalling ◽  
Energy Converting

Retrograde signalling refers to the regulation of nuclear gene expression in response to functional changes in organelles. In plants, the two energy-converting organelles, mitochondria and chloroplasts, are tightly coordinated to balance their activities. Although our understanding of components involved in retrograde signalling has greatly increased in the last decade, studies on the regulation of the two organelle signalling pathways have been largely independent. Thus, the mechanism of how mitochondrial and chloroplastic retrograde signals are integrated is largely unknown. Here, we summarize recent findings on the function of mitochondrial signalling components and their links to chloroplast retrograde responses. From this, a picture emerges showing that the major regulators are integrators of both organellar retrograde signalling pathways. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.

scholarly journals Abundance of the α-subunits of Gi1, Gi2 and Go in synaptosomal membranes from several regions of the rat brain is increased in hypothyroidism

1991 ◽  
Vol 275 (1) ◽  
pp. 183-186 ◽  
Author(s):  
M Orford ◽  
D Mazurkiewicz ◽  
G Milligan ◽  
D Saggerson
Keyword(s):  
G Protein ◽  
Signalling Pathways ◽  
Synaptosomal Membranes ◽  
Protein Subunits ◽  
Functional Changes ◽  
Alpha Subunits ◽  
The Central Nervous System ◽  
Quantitative Immunoblotting ◽  
The Brain ◽  
Α Subunits

1. Rats (4 weeks old) were made hypothyroid by treatment with propylthiouracil together with a low-iodine diet for a further period of 4 weeks. Synaptosomal membranes were obtained from six anatomical regions of the brain. 2. The abundances in these membranes of the G-protein alpha-subunits Gi1 alpha, Gi2 alpha and Go alpha were measured by quantitative immunoblotting. 3. Hypothyroidism significantly increased the abundances of all three G-protein subunits in membranes from the cerebral cortex and the striatum. In the medulla oblongata and the hippocampus the abundances of Gi2 alpha and Go alpha were increased significantly. By contrast, in the cerebellum only Go alpha was increased, and in the hypothalamus only Gi2 alpha was increased. 4. It is suggested that this up-regulation of G-protein abundances may modify signalling pathways and may contribute to the functional changes that are observed in the central nervous system in hypothyroidism.

Involvement of the HIF-1α and Wnt/β-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury

2013 ◽  
Vol 126 (2) ◽  
pp. 163-174 ◽  
Author(s):  
Ying-Ying Yang ◽  
Pei-Chang Lee ◽  
Yi-Tsau Huang ◽  
Wei-Ping Lee ◽  
Ying-Ju Kuo ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Elevated Serum ◽  
Liver Graft ◽  
Signalling Pathways ◽  
Protective Agent ◽  
Ischaemia Reperfusion Injury ◽  
Positive Effects ◽  
Ischaemia Reperfusion ◽  
Hepatic Congestion ◽  
Pre Treatment

Besides cardioprotective effects, the AT1R (angiotensin-II type 1 receptor) antagonist losartan protects the liver from IRI [IR (ischaemia/reperfusion) injury], but the mechanism has not been fully determined. The HIF (hypoxia inducible factor)-1α and Wnt/β-catenin signalling pathways have been reported to be involved in the mechanism of liver IRI. Therefore the aim of the present study was to determine whether the Wnt/HIF axis is part of the mechanism of the positive effect of AngII inhibition by losartan in liver IRI in rats. Various measurements were made in MCD/HF-NASH (methionine- and choline-deficient-diet/high-fat-diet-induced non-alcoholic steatohepatitis) rats with liver IRI. Acute losartan pre-administration markedly reversed the IR-suppressed levels of the hepatic-protective factors IL (interleukin)-6, IFN (interferon)-γ, Wnt3a, β-catenin and HIF-1α, and decreased hepatic blood flow and IR-elevated serum ALT (alanine aminotransferase), hepatic TNF (tumour necrosis factor)-α, IL-1α, hepatic congestion, vacuolization and necrosis, hepatic Suzuki IRI scores, necrotic index and levels of TBARS (thiobarbituric acid-reacting substances) in MCD/HF-NASH rats. Furthermore, acute Wnt3a pre-treatment significantly inhibited IR-elevated serum ALT, hepatic Suzuki IRI scores and TBARS, and restored the IR-depleted β-catenin/HIF-1α activity in MCD/HF-NASH rats. Simultaneous acute sFRP2 (secreted frizzled-related protein 2; a Wnt3a inhibitor) pre-treatment eliminated the losartan-related beneficial effects in MCD/HF-NASH rats with liver IRI, which was accompanied by a decrease in hepatic HIF-1α/β-catenin activity. Losartan-induced up-regulation of HIF-1α and Wnt/β-catenin signalling was associated with the recovery of IR-inhibited hepatic Bcl-2, Mn-SOD (manganese superoxide), Cu/Zn-SOD (copper/zinc superoxide) and GSH levels, and the suppression of IR-increased hepatic catalase and caspase 3/caspase 8 levels in MCD/HF-NASH rats. In conclusion, up-regulation of the HIF-1α and Wnt/β-catenin signalling pathways are part of the mechanism of the positive effects of losartan-related AngII inhibition in MCD/HF-NASH rats with liver IRI. Our study highlights the potential of the dual-organ protective agent losartan in NASH patients with steatotic livers and cardiovascular risk.

scholarly journals PECAM-1 preserves cardiac function in pressure overload-induced biomechanical stress

2021 ◽  
Author(s):  
Margaret E. McCormick ◽  
Mauricio Rojas ◽  
John Reader ◽  
Ellie Tzima
Keyword(s):  
Cell Adhesion ◽  
Cardiac Function ◽  
Fluid Shear Stress ◽  
Critical Role ◽  
Mechanical Strain ◽  
Pressure Overload ◽  
Capillary Density ◽  
Cardiac Remodelling ◽  
Cardiomyocyte Hypertrophy ◽  
Biomechanical Stress

AbstractBackgroundHaemodynamic forces play a critical role in proper development of the heart, however much less is known about the mechanisms that regulate cardiac remodelling and function in response to haemodynamic stress in the adult. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion and signalling molecule that has important roles in regulation of junctional integrity, transendothelial migration and mechanotransduction in response to fluid shear stress. Our previous work identified a role for PECAM-1 in regulating baseline cardiac function via regulation of endothelial-cardiomyocyte communication.MethodsThis study investigates the role of PECAM-1 in cardiac remodelling in response to biomechanical stress due to pressure overload induced by transaortic constriction (TAC).ResultsOur data reveal that loss of PECAM-1 is associated with systolic dysfunction that is further accentuated following TAC. Adaptive increases in cardiomyocyte cross-sectional area, capillary density and hypertrophic gene expression were all affected with loss of PECAM-1. In control mice, maintained cardiac function was associated with activation of the c-Jun NH(2)-terminal kinase (JNK) pathway, whereas PECAM-1 deletion significantly decreased JNK activation after pressure overload. Our data suggest that in the absence of PECAM-1 signalling, inadequate remodelling of the heart under increased mechanical strain leads to further deterioration of cardiac function, characterized by reduced cardiomyocyte hypertrophy, capillary density and defects in the JNK signalling pathway.ConclusionsOur study reveals a role for PECAM-1 in preservation of cardiac function in response to biomechanical stress induced by pressure overload.

Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals

2016 ◽  
Vol 130 (23) ◽  
pp. 2105-2120 ◽  
Author(s):  
Yanmei Chen ◽  
Chuanxi Zhang ◽  
Shuxin Shen ◽  
Shengcun Guo ◽  
Lintao Zhong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Marrow Cell ◽  
Cardiac Remodelling ◽  
Ischaemia Reperfusion

Appropriate ultrasound-targeted microbubble destruction (UTMD) treatment enhanced engraftment signals at 14 days post-ischaemia/reperfusion (post-I/R). Delayed bone marrow cell (BMC) transplantation combined with UTMD treatment attenuated post-infarction cardiac remodelling. Delayed BMC transplantation combined with UTMD treatment promoted angiogenesis, cardiomyogenesis and expansion of cardiac c-kit+ cells.

scholarly journals Altered Calcium Influx Pathways in Cancer-Associated Fibroblasts

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 680
Author(s):  
Francisco Sadras ◽  
Teneale A. Stewart ◽  
Mélanie Robitaille ◽  
Amelia A. Peters ◽  
Priyakshi Kalita-de Croft ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Transforming Growth Factor ◽  
Calcium Influx ◽  
Calcium Signalling ◽  
Signalling Pathways ◽  
Calcium Signal ◽  
Cancer Associated Fibroblasts ◽  
Functional Changes ◽  
Influx Pathways

Cancer-associated fibroblasts (CAFs) represent an important component of the tumour microenvironment and are implicated in disease progression. Two outstanding questions in cancer biology are how CAFs arise and how they might be targeted therapeutically. The calcium signal also has an important role in tumorigenesis. To date, the role of calcium signalling pathways in the induction of the CAF phenotype remains unexplored. A CAF model was generated through exogenous transforming growth factor beta 1 (TGFβ1) stimulation of the normal human mammary fibroblast cell line, HMF3S (HMF3S-CAF), and changes in calcium signalling were investigated. Functional changes in HMF3S-CAF calcium signalling pathways were assessed using a fluorescent indicator, gene expression, gene-silencing and pharmacological approaches. HMF3S-CAF cells demonstrated functionally altered calcium influx pathways with reduced store-operated calcium entry. In support of a calcium signalling switch, two voltage-gated calcium channel (VGCC) family members, CaV1.2 and CaV3.2, were upregulated in HMF3S-CAFs and a subset of patient-derived breast CAFs. Both siRNA-mediated silencing and pharmacological inhibition of CaV1.2 or CaV3.2 significantly impaired CAF activation in HMF3S cells. Our findings show that VGCCs contribute to TGFβ1-mediated induction of HMF3S-CAF cells and both transcriptional interference and pharmacological antagonism of CaV1.2 and CaV3.2 inhibit CAF induction. This suggests a potential therapeutic role for targeting calcium signalling in breast CAFs.

Decoding resistant hypertension signalling pathways

2017 ◽  
Vol 131 (23) ◽  
pp. 2813-2834 ◽  
Author(s):  
Ricardo Cambraia Parreira ◽  
Leandro Heleno Guimarães Lacerda ◽  
Rebecca Vasconcellos ◽  
Swiany Silveira Lima ◽  
Anderson Kenedy Santos ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Signalling Pathways ◽  
Transcriptional Level ◽  
Cardiovascular Damage ◽  
Current State ◽  
Cardiovascular Morbidity And Mortality ◽  
Non Coding Rnas ◽  
Therapeutic Tools

Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin–angiotensin–aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches.

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