Abstract 5939: Inhomogenous Regulation Of Matrix Metalloproteinases And Their Endogenous Inhibitors Intensifies Cardiac Fibrosis In Zucker Diabetic Fatty Rats

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tobias Graf ◽  
Karoline Hanke ◽  
Hendrik Sager ◽  
Sabine Fredersdorf ◽  
Christof Burgdorf ◽  
...  
Keyword(s):  
Visual Field ◽  
Matrix Metalloproteinases ◽  
Cardiac Fibrosis ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Heart Weight ◽  
Left Ventricular Myocardium ◽  
Regulation Of Expression ◽  
Endogenous Inhibitors ◽  
Zucker Diabetic Fatty Rats

AIM: Experimental and clinical studies have demonstrated that matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are upregulated in dilated failing hearts and involved in the development and progression of myocardial remodelling. However, changes in MMP and TIMP protein levels or activity in the diabetic heart has not yet been described. METHODS: Untreated male Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats were sacrificed at the age of 6 (prediabetic), 22 (diabetic) and 42 (late diabetes) weeks (wks) and body weight, total heart weight and plasma glucose were measured (n=7, each group). MMP-2, MMP-9 and TIMP-1 were quantified by Western blot analysis of total protein isolated from left ventricular tissue. Expression of MMP/TIMP mRNA was determined by quantitative PCR (Taqman ® ). Additionally paraffin sections of the left ventricular myocardium were stained with Sirius Red to quantify cardiac fibrosis in percent of visual field. RESULTS: (see table1 ) In summary, expression of myocardial MMP-2 and MMP-9 increased, whereas TIMP-1 decreased throughout life in diabetic and non-diabetic animals. However, expression of MMP-2 and MMP-9 was significantly diminished in ZDF compared to ZL rats during various stages of diabetes. TIMP-1 expression was lower in diabetic animals only in the prediabetic stage. Similar results were found in quantitative RT-PCR. The relative amount of fibrosis in left ventricular myocardium was markedly enhanced in late stage of diabetes (ZDF 41% fibrosis/visual field vs. ZL 18%). CONCLUSION: The observed results may play a distinctive role in the remodelling processes in late stages of disease. The regulation of expression of MMPs may, therefore, be a useful therapeutic strategy to manage diabetic cardiomyopathy. Table 1 )

Abstract P112: Decreased α-Myosin Expression is Associated with Left Ventricular Hypertrophy in Hypertensive Caribbean Vervets

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Chelsea C Weaver ◽  
Anthony Gutierrez ◽  
Jeffrey L Osborn
Keyword(s):  
Gene Expression ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Cardiac Fibrosis ◽  
Peripheral Resistance ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Protein Isoforms ◽  
Left Ventricular Myocardium ◽  
Human Heart Failure

Caribbean vervets ( Chlorocebus aethiops sabeus ) develop hypertension (HT; Systolic Blood Pressure ≥ 140 mmHg) in over 30% (125/345) of the outbred population. Elevated total peripheral resistance in HT increases cardiac afterload, which may lead to left ventricular hypertrophy (LVH) and cardiac remodeling. We hypothesize that prolonged spontaneous HT is associated with LVH, cardiac and aortic fibrosis, as well as differential transcription of myocardial contractile proteins. Vervets were characterized as HT (SBP = 170 ± 25.3 mmHg; n=125) or normotensive (NT, SBP = 99 ± 14.5 mmHg; n=148) using forearm plethysmography (ketamine sedated;15 mg/kg i.m.). Cardiomyocyte cross-sectional area was greater in HT compared to NT animals (HT 283 ± 52 μm 2 , n=9 vs NT 114 ± 8 μm 2 , n=10; p<0.01). Average collagen stained as a function of tissue area was similar in left ventricular myocardium of HT and NT animals (HT 14.17 ± 3.13% or 0.17/1.21 mm 2 , n=9 vs NT 12.22 ± 0.80% or 0.16/1.27 mm 2 , n=10; p>0.05). Aortic adventia collagen area was greater in HT compared to NT vervets (HT 66.12 ± 4.22% or 0.60/0.90 mm 2 , n=6 vs NT 54.53 ± 2.21% or 0.56/1.02 mm 2 , n=10; p<0.05). Total tissue collagen was estimated using a hydroxyproline assay. Collagen content was not different between HT and NT vervets for left ventricular myocardium (HT 194.02 ± 8.61 μg/mL, n=11 vs NT 201.70 ± 18.89 μg/mL, n=10; p=0.71) or aorta (HT 745.64 ± 44.49 μg/mL, n=11 vs NT 668.39 ± 31.06 μg/mL, n=11; p=0.17). Myosin gene expression (α and β) was estimated using RT-PCR of mRNA in left ventricular myocardium of NT (SBP = 98.91 ±10.89 mmHg; n=20) and HT (SBP = 171.51 ± 30.28 mmHg; n=17) vervets. α-myosin was downregulated in HT compared to NT vervets (HT RQ = 0.10 ± 0.03 vs. NT RQ = 0.22 ± 0.04; p<0.05), while β-myosin expression was not different (HT RQ = 0.22 ± 0.17 vs. NT RQ = 0.20 ± 0.16; p=0.83). Thus, spontaneous HT in outbred vervets induces LVH in response to factors other than cardiac fibrosis. Myosin gene expression may shift from α-myosin to other contractile protein isoforms, characteristic of human heart failure. In this nonhuman primate model, HT does not induce significant aortic fibrosis that may occur in aged animals. Future studies will further characterize contractile and pro-inflammatory proteins in LVH of spontaneous HT vervets.

scholarly journals Regulation of expression of myosin light chain 1 in the overloading human left ventricular myocardium

1990 ◽  
Vol 52 ◽  
pp. 249
Author(s):  
Kazuteru Fujimoto ◽  
Koichi Nakao ◽  
Toyoaki Murohara ◽  
Ken Okumura ◽  
Yasuhiro Morikami ◽  
...  
Keyword(s):  
Light Chain ◽  
Myosin Light Chain ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Regulation Of Expression

Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis

2004 ◽  
Vol 82 (12) ◽  
pp. 809-820 ◽  
Author(s):  
Jens Fielitz ◽  
Manuela Leuschner ◽  
Heinz Renee Zurbr�gg ◽  
Britta Hannack ◽  
Reinhard Pregla ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Aortic Stenosis ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium

scholarly journals Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Julian Mustroph ◽  
Julian Hupf ◽  
Maria J. Baier ◽  
Katja Evert ◽  
Christoph Brochhausen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Severe Disease ◽  
Interleukin 1 ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Mrna Levels ◽  
Tgf Β1

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.

scholarly journals Serum procollagens, structural and functional characteristics of the heart in prediction of cardiac fibrosis after myocardial infarction

2020 ◽  
pp. 75-82
Author(s):  
A.V. Osokina ◽  
◽  
V.N. Karetnikova ◽  
O.M. Polikutina ◽  
A.V. Ivanova ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Venous Blood ◽  
Myocardial Damage ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Lateral Part ◽  
Type I ◽  
St Segment Elevation

The aim of the research is to study the dynamics of fibrosing markers of C-terminal procollagen, type I propeptide (PICP) and N-terminal propeptide type III procollagen (PIIINP) in patients with ST-segment elevation myocardial infarction (STEMI); to identify possible correlation between concentration of PICP and PIIINP with the degree of cardiac fibrosis and diastolic dysfunction (DD) in a year after MI. Material and methods. The analyzed sample included STEMI patients with preserved contractility of the left ventricular myocardium (LV). During MI 1-st day the ejection fraction due to Simpson method was ≥50%. On the 1-st and 12-th days of the disease, as well as in a year, the concentration of PICP, PIIINP in venous blood serum was determined in all the studied participants. Standard echocardiographic study was performed with an assessment of LV diastolic function and determination of the following parameters: e’ (septal part displacement), Em (lateral part displacement), and IOLP (indexed left atrium volume). In a year after STEMI, all patients underwent magnetic resonance imaging (MRI) with a contrast agent to determine the severity of fibrotic myocardial damage. Results. PICP concentration significantly decreased by annual stage relative to hospital period (p <0.001). Changes in PIIINP concentration were revealed during the 1s-t and 12-th days (p <0.001), and during the 12-th day and a year (p = 0.002). Both markers showed increased values on the 1-st day of the disease and did not decrease throughout the study. According to MRI results, it turned out that 57% (n = 49) of the observed patients had no signs of cardiac fibrosis (CF) in a year after myocardial infarction, while 10.5% of patients had a lesion ≥ 16% (n = 9). Significant correlations were obtained between CF ≥16% and PIIINP concentration on the 12-th day of MI (r = 0.72, p = 0.041), between CF ≥16% and e’ (cm / s) on the 12-th day (r = -0.66, p = 0.006). Conclusion. One can assume that it is possible to reveal developing CF risk group and, therefore, the development of DD in a year after STEMI determining the concentration of fibrosis markers at hospital stage.

scholarly journals Effects of Telmisartan on Myocardial Protein Profiles in Hypertensive Rats

2021 ◽  
Vol 34 (3) ◽  
pp. 299-299
Author(s):  
Yu Feng ◽  
Man-li Zhou ◽  
Jian-zhang Wang ◽  
Jia-qi Zhang ◽  
Shu-le Qian ◽  
...  
Keyword(s):  
Heat Shock ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Sterile Water ◽  
Protein Profiles ◽  
Related Protein ◽  
Hypertensive Rats ◽  
Treatment Groups ◽  
Proteasome 26S

Abstract Background To investigate the effects of telmisartan on the protein profiles of the left ventricular myocardium in spontaneously hypertensive rats (SHR). Methods Sixteen SHR were randomly divided into control and telmisartan treatment groups. Rats were treated with sterile water (10 ml/kg) or telmisartan (4.33 mg/kg) by gavage for 12 weeks. Wistar-Kyoto (WKY) rats treated with sterile water (10 ml/kg) as controls. At the end of 12 weeks of control or telmisartan treatment, rats were sacrificed, and hearts were collected for protein preparations, isotope labeling, and mass spectrometric analysis. Results In total, there were 23 differentially expressed proteins in the left ventricular myocardium between control and telmisartan treatment groups in SHR. Compared with the telmisartan group, the upregulated proteins in the SHR were dual-specificity mitogen-activated protein kinase kinase 3-like, transgelin, and haptoglobin subtype 2. The downregulated proteins in the SHR were as follows: von Willebrand factor (fragment), kininogen 1, small ribonucleoprotein-related protein, fibrinogen beta chain, protein mass 3 (fragment), proteasome 26s, heat shock protein 27-related protein 1, tenascin X, fibronectin subtype 2, transferrin receptor protein, platelets 1, cathepsin L1, complement factor B, isoform CRA_b, fibrinogen isomer, immunoglobulin heavy chain (γ polypeptide), and α 1 antiprotease. Conclusions Telmisartan differentially regulates myocardial protein expression in hypertensive rats including heat shock protein 27, fibrinogen, fibronectin, proteasome 26s and transgelin, as well as proteins in biochemical, metabolic, and signal transduction pathways. These changes in protein expression may contribute to the antihypertrophic effects of telmisartan in hypertension.

scholarly journals Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yankun Lyu ◽  
Vipin K. Verma ◽  
Younjee Lee ◽  
Iosif Taleb ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Excitation Contraction Coupling ◽  
Transverse Tubular System ◽  
Contraction Coupling ◽  
Senescent Phenotype ◽  
Cellular Microstructure ◽  
T System

AbstractIt is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

scholarly journals Myxomatous Mitral Valve Disease with Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical and Functional Significance of the Coincidence

2021 ◽  
Vol 8 (2) ◽  
pp. 9
Author(s):  
Nina C. Wunderlich ◽  
Siew Yen Ho ◽  
Nir Flint ◽  
Robert J. Siegel
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Morphological Changes ◽  
Morphological Characteristics ◽  
Mitral Annulus ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Valve Disease ◽  
Left Ventricular Myocardium ◽  
Basal Portion

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed.

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