Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep

Cytokines are responsible for the modulation of immunological and inflammatory processes and play a significant role in the pathogenesis of coronary artery disease. We estimated the levels of pro-/anti-inflammatory cytokines in South Indian patients with coronary artery disease. The study population comprised of groups 1–3: 100 patients each with acute myocardial infarction, unstable angina, and stable angina, respectively, and group 4 (100 healthy controls). Cytokine levels (interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) were estimated by enzyme-linked immunosorbent assay (ELISA). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were significantly higher in patients from groups 1 and 2, than in group 3 and controls. Acute myocardial infarction patients exhibited higher serum levels of interleukin-10 compared with other groups and control subjects. Patients with unstable angina had significantly lower interleukin-10 concentrations than those with stable angina. The ratios of pro-/anti-inflammatory cytokines in all the study groups increased significantly when patients with unstable angina were compared to other groups. In patients with acute myocardial infarction, interleukin-10 and tumor necrosis factor-α levels showed significant correlation with established risk factors such as body mass index, blood pressure, and lipid levels. Acute myocardial infarction patients show elevation in proinflammatory and anti-inflammatory cytokines, while unstable angina is associated with low levels of serum interleukin-10. Higher levels of antiinflammatory cytokine interleukin-10 may be needed to provide protection in unstable angina. These cytokines are markers of coronary artery disease and may be used for the identification of high-risk patients with unstable angina/acute myocardial infarction.

Download Full-text

GW25-e0245 Effects of allogenic bone marrow mesenchymal stem cells modified by bcl-2 gene transplantation on cardiac dysfunction rabbits after acute myocardial infarction

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2014.06.163 ◽

2014 ◽

Vol 64 (16) ◽

pp. C34

Author(s):

Li Shuren ◽

Wang Man ◽

Gao Qing ◽

Li Shuren

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cardiac Dysfunction ◽

Allogenic Bone ◽

Allogenic Bone Marrow ◽

Marrow Mesenchymal Stem Cells

Download Full-text

Cardiac Myofibroblast and Fibrosis

10.20944/preprints202105.0432.v1 ◽

2021 ◽

Author(s):

Hitoshi Kurose

Keyword(s):

Myocardial Infarction ◽

Extracellular Matrix ◽

Single Cell ◽

Inflammatory Cytokines ◽

Cardiac Dysfunction ◽

New Technologies ◽

Pressure Overload ◽

Time Dependent ◽

Selective Isolation ◽

Number Of Cells

Fibroblasts are differentiated to myofibroblasts and produce collagen and other extracellular matrix when the heart is exposed to stresses. Myocardial infarction and pressure overload-induced hypertrophy are major stresses to induce differentiation of fibroblasts. Since collagen can compensate the missing tissue due to injury, appropriate production of collagen is beneficial for the injured heart against rupture. However, excessive deposition of collagen is called fibrosis and causes cardiac dysfunction. After fibroblasts are differentiated to myofibroblasts, myofibroblasts can further change their phenotypes. In addition, myofibroblasts are found to have a new function other than collagen production. Myofibroblasts have macrophage-like functions that engulf dead cells and secrete anti-inflammatory cytokines. So far, research on fibroblasts has been delayed due to the lack of available markers for selective isolation of fibroblasts. In recent years, it has become possible to genetically label fibroblasts, sequence the cells at single cell levels, and manipulate function or the number of cells. Based on new technologies, the origin of fibroblasts and myofibroblasts, time-dependent changes of fibroblast states after injury, and heterogeneity have been demonstrated. Here, I will introduce recent advances in fibroblasts and myofibroblasts.

Download Full-text

Small Endogeneous Peptide Mitigates Myocardial Remodeling in a Mouse Model of Cardioselective Galectin-3 Overexpression

Circulation Heart Failure ◽

10.1161/circheartfailure.121.008510 ◽

2021 ◽

Author(s):

Swati D. Sonkawade ◽

Saraswati Pokharel ◽

Badri Karthikeyan ◽

Minhyung Kim ◽

Shirley Xu ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Cardiac Magnetic Resonance Imaging ◽

Cardiac Dysfunction ◽

Resonance Imaging ◽

Galectin 3

Background: Myocardial Gal3 (galectin-3) expression is associated with cardiac inflammation and fibrosis. Increased Gal3 portends susceptibility to heart failure and death. There are no data reporting the causative role of Gal3 to mediate cardiac fibro-inflammatory response and heart failure. Methods: We developed a cardioselective Gal3 gain-of-function mouse ( Gal3+/+ ) using α-myosin heavy chain promotor. We confirmed Gal3-transgene expression with real-time polymerase chain reaction and quantified cardiac/circulating Gal3 with Western blot and immunoassays. We used echocardiogram and cardiac magnetic resonance imaging to measure cardiac volumes, function, and myocardial velocities. Ex vivo, we studied myocardial inflammation/fibrosis and downstream TGF (transforming growth factor) β1-mRNA expression. We examined the effects of acute myocardial ischemia in presence of excess Gal3 by inducing acute myocardial infarction in mice. Two subsets of mice including mice treated with N-acetyl-seryl-aspartyl-lysyl-proline (a Gal3-inhibitor) and mice with genetic Gal3 loss-of-function ( Gal3 −/−) were studied for comparative analysis of Gal3 function. Results: Gal3+/+ mice had increased cardiac/circulating Gal3. Gal3+/+ mice showed excess pericardial fat pad, dilated ventricles and cardiac dysfunction, which was partly normalized by N-acetyl-seryl-aspartyl-lysyl-proline. Cardiac magnetic resonance imaging showed reduced myocardial contractile velocities in Gal3+/+ . The majority of Gal3+/+ mice did not survive acute myocardial infarction, and the survivors had profound cardiac dysfunction. Myocardial histology of Gal3+/+ mice showed macrophage/mast-cell infiltration, fibrosis and higher TGFβ1-mRNA expression, which were mitigated by both Gal3 gene deletion and N-acetyl-seryl-aspartyl-lysyl-proline administration. Conclusions: Our study shows that cardioselective Gal3 overexpression leads to multiple cardiac phenotypic defects including ventricular dilation and cardiac dysfunction. Pharmacological Gal3 inhibition conferred protective effects with reduction of inflammation and fibrosis. Our study highlights the importance of translational studies to counteract Gal3 function and prevent cardiac dysfunction.

Download Full-text