scholarly journals Left-Ventricular Remodeling After Myocardial Infarction Is Associated with a Cardiomyocyte-Specific Hypothyroid Condition

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 669-679 ◽  
Author(s):  
Christine J. Pol ◽  
Alice Muller ◽  
Marian J. Zuidwijk ◽  
Elza D. van Deel ◽  
Ellen Kaptein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Luciferase Reporter ◽  
Cardiomyocyte Hypertrophy ◽  
In Vivo Measurement ◽  
Pathological Remodeling

Abstract Similarities in cardiac gene expression in hypothyroidism and left ventricular (LV) pathological remodeling after myocardial infarction (MI) suggest a role for impaired cardiac thyroid hormone (TH) signaling in the development of heart failure. Increased ventricular activity of the TH-degrading enzyme type 3 deiodinase (D3) is recognized as a potential cause. In the present study, we investigated the cardiac expression and activity of D3 over an 8-wk period after MI in C57Bl/6J mice. Pathological remodeling of the noninfarcted part of the LV was evident from cardiomyocyte hypertrophy, interstitial fibrosis, and impairment of contractility. These changes were maximal and stable from the first week onward, as was the degree of LV dilation. A strong induction of D3 activity was found, which was similarly stable for the period examined. Plasma T4 levels were transiently decreased at 1 wk after MI, but T3 levels remained normal. The high D3 activity was associated with increased D3 mRNA expression at 1 but not at 4 and 8 wk after MI. Immunohistochemistry localized D3 protein to cardiomyocytes. In vivo measurement of TH-dependent transcription activity in cardiomyocytes using a luciferase reporter assay indicated a 48% decrease in post-MI mice relative to sham-operated animals, and this was associated with a 50% decrease in LV tissue T3 concentration. In conclusion, pathological ventricular remodeling after MI in the mouse leads to high and stable induction of D3 activity in cardiomyocytes and a local hypothyroid condition.

scholarly journals Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiuyu Chen ◽  
Minjie Lu ◽  
Ning Ma ◽  
Gang Yin ◽  
Chen Cui ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cine Mri ◽  
Control Group

Purpose.To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner.Materials and Methods.Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively.Results.MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation.Conclusions.Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI.

Abstract 18200: Intracoronary Delivery of Bioabsorbable Alginate Matrix (IK-5001) Ameliorates Adverse Post-infarction Left Ventricular Remodeling and Improves Left Ventricular Function in a Porcine Model of Reperfused Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Carlos G Santos-Gallego ◽  
Belén Picatoste ◽  
Ida U Njerve ◽  
Kiyotake Ishikawa ◽  
Jaime Aguero ◽  
...  
Keyword(s):  
Porcine Model ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Function ◽  
Contractile Reserve ◽  
Intracoronary Injection ◽  
Lv Remodeling

Background: Adverse cardiac remodeling after MI is associated with excessive degradation of the extracellular matrix (ECM). IK-5001 is a low viscosity injectable solution that provides the polysaccharide alginate. After intracoronary injection into the MI area it undergoes phase transition forming a hydrogel which can support the ECM. We hypothesized that administration of alginate post-MI would provide a temporary scaffold and attenuate adverse LV remodeling. Methods: Acute MI was induced in 16 pigs by balloon occlusion of the proximal LAD for 2 hours. Animals randomly received intracoronary alginate or saline 4 days post-MI. LV function and remodeling were evaluated with cardiac MRI, 3D-echo and pressure-volume loops at 1 and 2 months post-MI. Histology and Western blot analysis were performed after 2 months. Results: Both groups had similar LVEF and infarct size 4 days post-MI. Coronary angiography immediately after alginate injection showed no impairment in coronary flow. However, 2 months post-MI, alginate-treated pigs exhibited reduced LV remodeling compared with controls demonstrated by reduced LV end-systolic volume, LV mass and sphericity (Table). Alginate-treated pigs had less cardiomyocyte hypertrophy and decreased interstitial fibrosis. Consistent with this, chronic activation of Akt and ERK was reduced. Alginate pigs also showed lower plasma levels of BNP and aldosterone. Interestingly, after 2 months, alginate pigs showed better systolic LV function: higher LVEF, better contractile reserve with dobutamine, and higher dP/dt. Conclusions: Intracoronary administration of alginate ameliorates adverse post-MI LV remodeling at the anatomical, histological and molecular level, and mitigates neurohormonal activation in a porcine model of MI. Alginate also improves systolic LV function. Intracoronary injection of alginate represents an exciting novel treatment option to reduce post-MI remodeling that merits assessment in clinical studies.

Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction

2017 ◽  
Vol 112 (3) ◽  
Author(s):  
Thomas Ravn Lassen ◽  
Jan Møller Nielsen ◽  
Jacob Johnsen ◽  
Steffen Ringgaard ◽  
Hans Erik Bøtker ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Rat Model ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular

scholarly journals Hydrogen Sulfide Reduces Recruitment of CD11b+DG Gr-1+DG Cells in Mice with Myocardial Infarction

2017 ◽  
Vol 26 (5) ◽  
pp. 753-764 ◽  
Author(s):  
Ting Wu ◽  
Hua Li ◽  
Bing Wu ◽  
Lei Zhang ◽  
San-Wu Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Sodium Hydrosulfide ◽  
Therapeutic Benefits

The present study aimed to elucidate the mechanisms by which hydrogen sulfide (H2S) attenuates left ventricular remodeling after myocardial infarction (MI). MI was created in mice by left coronary artery ligation. One group of mice received injections of the H2S donor sodium hydrosulfide (NaHS) immediately before and 1 h after ligation, while the control group received saline alone. During both the subacute and chronic stages (1 and 4 weeks postinfarction, respectively), NaHS-treated mice demonstrated attenuation of cardiac dilation in the infarcted myocardium. Furthermore, fewer CD11b+Gr-1+ myeloid cells were detected in the infarct myocardium and peripheral blood from NaHS-treated mice, while more CD11b+ Gr-1+ cells remained in the spleen and bone marrow in these animals. NaHS-treated mice also exhibited reduction in cardiomyocyte apoptosis, interstitial fibrosis, cardiac hypertrophy, and pulmonary edema, as well as overall better survival rates, when compared to controls. Thus, exogenous H2S has favorable effects on cardiac remodeling after MI. These observations further support the emerging concept that H2S treatment might have therapeutic benefits in the setting of ischemia-induced heart failure.

scholarly journals Decreased metalloprotease 9 induction, cardiac fibrosis, and higher autophagy after pressure overload in mice lacking the transcriptional regulator p8

2011 ◽  
Vol 301 (5) ◽  
pp. C1046-C1056 ◽  
Author(s):  
Serban P. Georgescu ◽  
Mark J. Aronovitz ◽  
Juan L. Iovanna ◽  
Richard D. Patten ◽  
John M. Kyriakis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Pressure Overload ◽  
Transcriptional Regulator ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Causative Role

Left ventricular remodeling, including the deposition of excess extracellular matrix, is key to the pathogenesis of heart failure. The stress-inducible transcriptional regulator p8 is increased in failing human hearts and is required both for agonist-stimulated cardiomyocyte hypertrophy and for cardiac fibroblasts matrix metalloprotease-9 (MMP9) induction. In the heart, upregulation of autophagy is an adaptive response to stress and plays a causative role in cardiomyopathies. We have recently shown that p8 ablation in cardiac cells upregulates autophagy and that, in vivo, loss of p8 results in a decrease of cardiac function. Here we investigated the effects of p8 genetic deletion in mediating adverse myocardial remodeling. Unstressed p8−/− mouse hearts manifested complex alterations in the expression of fibrosis markers. In addition, these mice displayed elevated autophagy and apoptosis compared with p8+/+ mice. Transverse aortic constriction (TAC) induced left ventricular p8 expression in p8+/+ mice. Pressure overload caused left ventricular remodeling in both genotypes, however, p8−/− mice showed less cardiac fibrosis induction. Consistent with this, although MMP9 induction was attenuated in the p8−/− mice, induction of MMP2 and MMP3 were strikingly upregulated while TIMP2 was downregulated. Left ventricular autophagy increased after TAC and was significantly higher in the p8−/− mice. Thus p8-deletion results in reduced collagen fibrosis after TAC, but in turn, is associated with a detrimental higher increase in autophagy. These findings suggest a role for p8 in regulating in vivo key signaling pathways involved in the pathogenesis of heart failure.

Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice

2010 ◽  
Vol 298 (3) ◽  
pp. H1072-H1078 ◽  
Author(s):  
Tomohiro Nishioka ◽  
Katsuya Onishi ◽  
Naoshi Shimojo ◽  
Yuka Nagano ◽  
Hidenori Matsusaka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
High Serum ◽  
Border Zone ◽  
Myocardial Stiffness ◽  
Tenascin C

Tenascin-C (TN-C) is an extracellular matrix glycoprotein with high bioactivity. It is expressed at low levels in normal adult heart, but upregulated under pathological conditions, such as myocardial infarction (MI). Recently, we (Ref. 34 ) reported that MI patients with high serum levels of TN-C have a greater incidence of maladaptive cardiac remodeling and a worse prognosis. We hypothesized that TN-C may aggravate left ventricular remodeling. To examine the effects of TN-C, MI was induced by ligating coronary arteries of TN-C knockout (KO) mice under anesthesia and comparing them with sibling wild-type (WT) mice. In WT+MI mice, TN-C expression was upregulated at day 1, peaked at day 5, downregulated and disappeared by day 28, and the molecule was localized in the border zone between intact myocardium and infarct lesions. The morphometrically determined infarct size and survival rate on day 28 were comparable between the WT+MI and KO+MI groups. Echocardiography and hemodynamic analyses demonstrated left ventricular end-diastolic diameter, myocardial stiffness, and left ventricular end-diastolic pressure to be significantly increased in both WT+MI and KO+MI mice compared with sham-operated mice. However, end-diastolic pressure and dimension and myocardial stiffness of KO+MI were lower than those of the WT+MI mice. Histological examination revealed normal tissue healing, but interstitial fibrosis in the residual myocardium in peri-infarcted areas was significantly less pronounced in KO+MI mice than in WT+MI mice. TN-C may thus accelerate adverse ventricular remodeling, cardiac failure, and fibrosis in the residual myocardium after MI.

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