Mitochondrial apoptotic pathway activation in the atria of heart failure patients due to mitral and tricuspid regurgitation

Chang, Jen‐Ping; Chen, Mien‐Cheng; Liu, Wenhao; Lin, Yu‐Sheng; Huang, Yao‐Kuang; Pan, Kuo‐Li; Ho, Wan-Chun; Fang, Chih-Yuan; Chen, Chien-Jen; Chen, Huang‐Chung

doi:10.1016/j.yexmp.2015.05.007

Cited by 6 publications

(5 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Volume overload caused by MR induces atrial myocyte stretching, which then causes left atrial dilatation. In MR patients, altered mitochondrial function and reactive oxidative stress overproduction in the atria [16,17] altered fatty acid β-oxidation and lipid metabolism. Moreover, lipid expression of atrial myocytes in the left atria is significantly higher in MR patients compared to normal controls and compared to patients with aortic valve disease [14].…”

Section: Discussionmentioning

confidence: 99%

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Fang

Chen

Chang

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

Background: Lipid expression is increased in the atrial myocytes of mitral regurgitation (MR) patients. This study aimed to investigate key regulatory genes and mechanisms of atrial lipotoxic myopathy in MR. Methods: The HL-1 atrial myocytes were subjected to uniaxial cyclic stretching for eight hours. Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism were analyzed by PCR assay (168 genes). Results: The stretched myocytes had significantly larger cell size and higher lipid expression than non-stretched myocytes (all p < 0.001). Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism in the myocytes were analyzed by PCR assay (168 genes). In comparison with their counterparts in non-stretched myocytes, seven genes in stretched monocytes (Idi1, Olr1, Nr1h4, Fabp2, Prkag3, Slc27a5, Fabp6) revealed differential upregulation with an altered fold change >1.5. Nine genes in stretched monocytes (Apoa4, Hmgcs2, Apol8, Srebf1, Acsm4, Fabp1, Acox2, Acsl6, Gk) revealed differential downregulation with an altered fold change <0.67. Canonical pathway analysis, using Ingenuity Pathway Analysis software, revealed that the only genes in the “superpathway of cholesterol biosynthesis” were Idi1 (upregulated) and Hmgcs2 (downregulated). The fraction of stretched myocytes expressing Nile red was significantly decreased by RNA interference of Idi1 (p < 0.05) and was significantly decreased by plasmid transfection of Hmgcs2 (p = 0.004). Conclusions: The Idi1 and Hmgcs2 genes have regulatory roles in atrial lipotoxic myopathy associated with atrial enlargement.

show abstract

Section: Discussionmentioning

confidence: 99%

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Fang

Chen

Chang

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…To investigate the apoptotic events of IA mice model, the present study investigated the mRNA expression of caspases associated with the mitochondrial apoptotic pathway, including caspase-3, -8 and -9. The activation of caspases serves an essential role during the process of apoptosis (39), which may be caused by an extrinsic or intrinsic pathway, which lead to a terminal common pathway (40). Caspase-8 activation is involved in the extrinsic pathway and caspase-9 is involved in the intrinsic pathway.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑29a contributes to intracranial aneurysm by regulating the mitochondrial apoptotic pathway

Zhao

Zhang

2018

Mol Med Report

View full text Add to dashboard Cite

Intracranial aneurysm (IA) is an abnormal expansion in the intracranial arteries that weakens the arterial wall by consistently pushing the vascular wall outwards, which leads to a higher risk of aneurysm rupture. A number of reports have demonstrated that apoptosis is associated with the growth and rupture of IA. MicroRNAs (miRNAs/miRs) perform vital roles in the regulation of the mitochondrial apoptotic pathway and signaling proteins. Increasing evidence has already revealed the role of miR‑29a in injury, including liver injury, cardiovascular injury and ischaemia‑reperfusion injury. However, the role of miR‑29a in IA remains unclear at present. The present study investigated the role of miR‑29a in IA pathogenesis and the underlying mechanisms. By using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, the present study demonstrated that genes, including caspase‑3, ‑8 and ‑9, and proteins, including cytochrome c and myeloid cell leukemia 1 (Mcl‑1), involved in mitochondrial apoptosis pathways were upregulated in IA groups compared with controls. In addition, microarray analysis demonstrated that miR‑29a, one of the most altered miRs in IA mice, was overexpressed in IA mice compared with controls. In vitro experiments revealed that miR‑29a downregulation attenuated human brain vascular smooth muscle cell (HBVSMC) apoptosis, while miR‑29a overexpression increased the apoptosis of HBVSMCs. Furthermore, luciferase reporter analysis revealed that Mcl‑1 is a direct target gene of miR‑29a. An in vivo IA model confirmed that miR‑29a overexpression may promote apoptosis through mitochondrial pathways. It was therefore concluded that miR‑29a may contribute to the progression of IA by regulating mitochondrial apoptotic pathways. Thus, miR‑29a is a potential therapeutic target for IA.

show abstract

“…However, altered expression of the fatty acid oxidation enzymes can impair mitochondrial metabolism and lead to pathologic remodeling of myocardium, probably through lipotoxicity, reactive oxidative stress overproduction, and ATP deficiency [ 9 – 11 ]. Our prior studies showed that altered mitochondrial function and reactive oxidative stress overproduction due to nox2 containing NADPH oxidase activity developed in the atria of MR patients with heart failure [ 12 , 13 ]. Moreover, heart-specific overexpression of PPAR induced several target genes involved in fatty acid utilization and increased cardiac fatty acid uptake and oxidation [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Taken together, this study demonstrated that the altered expression of ACADM, FABP3, ECH1, ACAA2, EHHADH, CPT1A and PLTP of the PPAR signaling pathway in the left atria of MR patients compared to patients with aortic valve disease and normal controls should play a substantially role in the altered fatty acid metabolism (Fig. 3 ), glucose metabolism, energy utilization, and pathologic remodeling (hypertrophy, myolysis, glycogen accumulation, apoptosis, autophagy and inflammation) in the atria of MR patients, either partly through altered mitochondrial function, reactive oxidative stress overproduction, inflammation and apoptosis or partly as an adaptive response to volume overload of MR [ 3 , 4 , 12 , 13 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundDifferentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored.MethodsThis study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria.ResultsGene expression profiling analysis through PCR assay identified 23 genes to be differentially expressed in the left atria of MR patients compared to normal controls. The expressions of APOA1, ACADM, FABP3, ETFDH, ECH1, CPT1B, CPT2, SLC27A6, ACAA2, SMARCD3, SORBS1, EHHADH, SLC27A1, PPARGC1B, PPARA and CPT1A were significantly up-regulated, whereas the expression of PLTP was significantly down-regulated in the MR patients compared to normal controls. The expressions of HMGCS2, ACADM, FABP3, MLYCD, ECH1, ACAA2, EHHADH, CPT1A and PLTP were significantly up-regulated in the MR patients compared to patients with aortic valve disease. Notably, only ACADM, FABP3, ECH1, ACAA2, EHHADH, CPT1A and PLTP of the PPAR pathway were significantly differentially expressed in the MR patients compared to patients with aortic valve disease and normal controls.ConclusionsDifferentially expressed genes of the PPAR pathway have been identified in the left atria of MR patients compared with patients with aortic valve disease and normal controls.

show abstract

Mitochondrial apoptotic pathway activation in the atria of heart failure patients due to mitral and tricuspid regurgitation

Cited by 6 publications

References 22 publications

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

MicroRNA‑29a contributes to intracranial aneurysm by regulating the mitochondrial apoptotic pathway

Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation

Contact Info

Product

Resources

About