P2582Signature of plasma extracellular vesicles associated proteins in acute myocardial infarction patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J W Wang ◽  
S M J M Yatim ◽  
X C Lim ◽  
S Y Chong ◽  
X Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Healthy Subjects ◽  
Structural Equation ◽  
Longitudinal Data Analysis ◽  
Equation Model ◽  
Left Ventricular ◽  
Protein Levels ◽  
Lv Remodeling ◽  
Associated Proteins ◽  
Multi Level

Abstract Background Prediction of left ventricular (LV) remodeling post-acute myocardial infarction (AMI) remains challenging. Several circulating biomarkers have been associated with post-AMI LV remodeling, however, there is no biomarker available to distinguish adverse versus reverse LV remodeling. Purpose In this study, we aimed to assess the association of extracellular vesicles (EVs) associated proteins with LV remodeling post-AMI. Methods Plasma EVs were isolated via precipitation with dextran sulphate as we previously reported. The protein levels of EV associated von Willebrand factor (VWF), SerpinC1 (antithrombin-III), plasminogen and SerpinF2 (alpha 2-antiplasmin) were determined in the citrate-anticoagulated plasma from 57 healthy subjects and 200 patients recruited in the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study. Patients were categorized into two groups: adverse LV remodeling (n=100) characterized by an increase or reverse LV remodeling (n=100) characterized by a decrease, in LV end systolic volume by ≥15% over 6 months. Patients' plasma was collected at baseline (within 3 days after percutaneous coronary intervention), 1 month and 6 months post-AMI. Log transformation of EV protein levels was performed for assessment in a multiple multi-level longitudinal data analysis with structural equation model (with level of significance fixed at 0.05). Results Compared to healthy subjects, baseline protein levels of EV associated VWF and SerpinF2 were significantly higher in post-AMI patients, whereas no difference was observed in SerpinC1 and plasminogen. Among the patients, those on statins (196 out of 200 patients) showed lower protein levels of EV associated VWF (p<0.001) and plasminogen (p=0.003), whereas patients treated with P2Y12 platelet inhibitors (195 out of 200 patients) showed higher protein levels of EV associated VWF (p=0.003) and plasminogen (p=0.035). Multiple multi-level longitudinal data analysis with structural equation model showed that protein levels of EV associated VWF (p<0.001) and SerpinC1 (p=0.021) were lower in patients with adverse LV remodeling than that in patients with reverse LV remodeling during the 6-month follow-up post-AMI. In contrast, protein levels of EV associated plasminogen (p=0.002) and SerpinF2 (p=0.002) were higher in patients with adverse LV remodeling. The differences in the four EV associated proteins between patients with adverse versus reverse LV remodeling remain significant after adjusting for age, gender, ethnicity, medications, lipid profile and risk factors (diabetes, hypertension, dyslipidemia and smoking). Conclusions Lower levels of EV associated coagulation proteins (VWF and SerpinC1) and higher levels of EV associated fibrinolytic proteins (plasminogen and SerpinF2) were presented in patients with adverse LV remodeling compared to those with reverse LV remodeling post-AMI. Acknowledgement/Funding National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang

P4639Plasma tissue factor coagulation activity in post-acute myocardial infarction patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
X C Lim ◽  
S M J M Yatim ◽  
S Y Chong ◽  
X Wang ◽  
S H Tan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Plasma Levels ◽  
Healthy Subjects ◽  
Left Ventricular ◽  
Mean Difference ◽  
Coagulation Activity ◽  
Systolic Volume ◽  
Lv Remodeling ◽  
End Systolic Volume

Abstract Background Coagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. Purpose We aimed to evaluate the association of plasma tissue factor (TF) coagulation activity with LV remodeling prior to heart failure in post-AMI patients. Methods This study was conducted in 228 subjects from the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study and 57 healthy subjects. The post-AMI patients were divided into two age- and sex-matched groups: patients with adverse LV remodeling defined as an increase in LV end systolic volume by ≥15% over 6 months and patients with reverse LV remodeling defined as an decrease in LV end systolic volume by ≥15% over 6 months. TF coagulation activity was determined using human coagulation factor Xa generation based TF chromogenic activity assay and converted into concentrations of active TF (pM). Sodium-citrate anticoagulated plasma was collected at baseline (within 3 days after revascularization), 30 days and 6 months post-AMI. Results are presented as mean±S.E.M. One-way or two-way repeated measures ANOVA or a multiple multi-level longitudinal data analysis with structural equation model was used to assess differences in coagulation activity. P<0.05 was considered statistically significant. Results Plasma from healthy subjects and post-AMI patients at baseline had similar concentrations of active TF (TFa): 29.0±1.4 versus 29.1±0.7 pM. Patients treated with warfarin (15 out of 228 patients) showed lower plasma levels of TFa (mean difference −15.2 pM, [95% CI: −18.7, −11.7], p<0.001). Compared to baseline, plasma levels of TFa in the patients was significantly lower at 30 days post-AMI (mean difference −6.9 pM, [95% CI: −4.8, −8.9], p<0.001) and 6 months post-AMI (mean difference −2.8 pM, [95% CI: −0.8, −4.8], p=0.003). Intriguingly, plasma levels of TFa tended to recover from 30 days to 6 months post-AMI (mean difference 4.1 pM, [95% CI: 2.8, 5.4], p<0.001) toward the baseline level and the level in healthy subjects. Similar trends of temporal changes of plasma TFa levels were observed in patients with adverse LV remodeling and those with reverse LV remodeling although TFa levels were slightly higher in patients with reverse LV remodeling (F(2,448)=3.112, p=0.045 for interaction). After adjusting for age, gender, ethnicity, medications, lipid profile and risk factors, the temporal changes of plasma TFa levels in patients remain significant, however, the difference between patients with adverse versus reverse LV remodeling was not significant. Conclusion Plasma TF coagulation activity decreased post-AMI but did not differ in patients with adverse versus reverse LV remodeling. Acknowledgement/Funding National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang

Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling

Cardiology ◽  
2017 ◽  
Vol 138 (2) ◽  
pp. 91-96 ◽  
Author(s):  
Sam C. Latet ◽  
Paul L. Van Herck ◽  
Marc J. Claeys ◽  
Amaryllis H. Van Craenenbroeck ◽  
Steven E. Haine ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Healthy Subjects ◽  
Noncoding Rna ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Circulating Microrna ◽  
Second Phase ◽  
End Diastolic Volume ◽  
Lv Remodeling ◽  
St Elevation

Background: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. Aims: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). Methods: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. Results: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). Conclusion: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Detrimental effect of combined exercise training and eNOS overexpression on cardiac function after myocardial infarction

2009 ◽  
Vol 296 (5) ◽  
pp. H1513-H1523 ◽  
Author(s):  
Monique C. de Waard ◽  
Jolanda van der Velden ◽  
Nicky M. Boontje ◽  
Dick H. W. Dekkers ◽  
Rien van Haperen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Exercise Training ◽  
Left Ventricular ◽  
Lv Function ◽  
Enos Expression ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Enos Uncoupling ◽  
Lv Remodeling ◽  
Exercise Induced

It has been reported that exercise after myocardial infarction (MI) attenuates left ventricular (LV) pump dysfunction by normalization of myofilament function. This benefit could be due to an exercise-induced upregulation of endothelial nitric oxide synthase (eNOS) expression and activity. Consequently, we first tested the hypothesis that the effects of exercise after MI can be mimicked by elevated eNOS expression using transgenic mice with overexpression of human eNOS (eNOSTg). Both exercise and eNOSTg attenuated LV remodeling and dysfunction after MI in mice and improved cardiomyocyte maximal force development (Fmax). However, only exercise training restored myofilament Ca2+-sensitivity and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a protein levels and improved the first derivative of LV pressure at 30 mmHg. Conversely, only eNOSTg improved survival. In view of these partly complementary actions, we subsequently tested the hypothesis that combining exercise and eNOSTg would provide additional protection against LV remodeling and dysfunction after MI. Unexpectedly, the combination of exercise and eNOSTg abolished the beneficial effects on LV remodeling and dysfunction of either treatment alone. The latter was likely due to perturbations in Ca2+ homeostasis, as myofilament Fmax actually increased despite marked reductions in the phosphorylation status of several myofilament proteins, whereas the exercise-induced increases in SERCA2a protein levels were lost in eNOSTg mice. Antioxidant treatment with N-acetylcysteine or supplementation of tetrahydrobiopterin and l-arginine prevented these detrimental effects on LV function while partly restoring the phosphorylation status of myofilament proteins and further enhancing myofilament Fmax. In conclusion, the combination of exercise and elevated eNOS expression abolished the cardioprotective effects of either treatment alone after MI, which appeared to be, at least in part, the result of increased oxidative stress secondary to eNOS “uncoupling.”

Cardiac magnetic resonance T1 mapping allows for predicting adverse left ventricular remodeling post-reperfused st-elevation myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Zhang ◽  
Y.K Guo ◽  
Z.G Yang ◽  
M.X Yang ◽  
K.Y Diao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T1 Mapping ◽  
Ventricular Remodeling ◽  
Tissue Injury ◽  
Left Ventricular ◽  
Funding Source ◽  
Native T1 ◽  
End Diastolic Volume ◽  
Significant Difference ◽  
Lv Remodeling

Abstract Background Cardiac magnet resonance (CMR) T1 mapping allows the quantitative characterization of the severity of tissue injury and predict functional recovery in acute myocardial infarction (AMI). Purpose The study aimed to investigate whether native T1 and ECV of infarct myocardium are influenced by microvascular obstruction (MVO) and have predictive value for adverse left ventricular (LV) remodeling post-infarction. Method A cohort of 54 patients with successfully reperfused STEMI underwent CMR imaging at a 3T scanner in AMI and 3 months post-infarction. Native T1 data was acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, and ECV maps were calculated using blood sampled hematocrit. Manual regions-of-interest were drawn within the infarct myocardium to measure native T1 and ECV (native T1infarct and ECVinfarct, respectively). MVO identified as a low-intensity area within the infarct zone on LGE was eliminated. Results MVO was present in 36 patients (66.67%) in AMI. ECVinfarct in patients with MVO was different from those without (58.66±8.71% vs. 49.64±8.82%, P=0.001), while no significant difference in T1infarct was observed between patients with and without MVO (1474.7±63.5ms vs. 1495.4±98.0ms, P=0.352). ECV correlated well with the change in end-diastolic volume (all patients: r=0.564, P&lt;0.001) and predicted LV remodeling in patients with and without MVO (rMVO absent = 0.626, P=0.005; rMVO present = 0.686, P&lt;0.001; all patients: r=0.622, P&lt;0.001); Native T1 was only associated with a 3-month change in LV end-diastolic volume (rMVO absent= 0.483, P=0.042) and predicted LV remodeling in patients without MVO (rMVO absent = 0.659, P=0.003). Furthermore, ECV had an association with LV remodeling (β=0.312, P=0.007) in multivariable logistic analysis. Conclusion Absolute native T1 in infarct myocardium might be affected by MVO but ECV isn't. ECV could predict LV remodeling in MI patients with and without MVO, while native T1 predict it in MI with MVO absent. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University

Interferon-gamma inducible protein IP-10 and left ventricular remodelling post-acute myocardial infarction: a longitudinal cardiovascular magnetic resonance imaging substudy of CAPRI clinical trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Sopova ◽  
C Park ◽  
A Al-Atta ◽  
K Bennaceur ◽  
A Mohammad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Regression Analysis ◽  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Linear Regression Analysis ◽  
Left Ventricular ◽  
Lv Remodeling ◽  
Inducible Protein ◽  
Cmr Imaging

Abstract Background Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown. Purpose To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI). Methods This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study. Results Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P&lt;0.001 for all). Comparison of the 12-week CMR to the baseline CMR imaging revealed that baseline pre-reperfusion as well as 5min, 15min, 30min and 90min, but not 24h, post-reperfusion IP-10 serum levels associated with increased LVEF and decreased ESV at 12-weeks (range correlation coefficient r=[0.35–0.41], P&lt;0.05 with ΔLVEF and r=[−0.33 to −0.44], P&lt;0.05 with ΔESV) indicating that the increase of IP-10 at the acute phase of myocardial infarction confers a cardioprotective role. Multivariable linear regression analysis for ΔLVEF showed that in a model including baseline pre-reperfusion or 5min or 15min or 30min or 90min post-reperfusion IP-10 and age, gender, traditional risk factors (arterial hypertension, body-mass index, hyperlipoproteinemia, diabetes mellitus, smoking, family history of CAD), infarct location, admission high-sensitivity troponin T, door-to-balloon time and ciclosporin treatment, only IP-10 was the independent determinant of ΔLVEF. Conclusions Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated. Funding Acknowledgement Type of funding source: None

Abstract 5393: Increased C-Reactive Protein Expression Exacerbates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Toshiyuki Takahashi ◽  
Toshihisa Anzai ◽  
Hidehiro Kaneko ◽  
Atsushi Anzai ◽  
Yoshinori Mano ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Border Zone ◽  
Histological Evaluation ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Lv Remodeling

We have previously reported that elevated serum C-reactive protein (CRP) level after acute myocardial infarction (MI) is associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling and cardiac death. Recent experimental studies have shown that CRP per se has some biological properties including proinflammatory and proapoptotic effects, suggesting a pathogenetic role of CRP in the remodeling process after MI. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI through some deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their nontransgenic littermates (Control) underwent proximal ligation of the left coronary artery. Despite increased serum CRP level and cardiac CRP expression in CRP-Tg mice, there was no difference in phenotype between CRP-Tg and control mice before MI. Mortality at five weeks after MI was not different between groups (CRP-Tg: 49%, n=35; Control: 38%, n=40, P =0.28). Five weeks after MI, echocardiography showed that CRP-Tg mice had more LV dilation (LVEDD, CRP-Tg: 5.8 ± 0.1 mm, n=14; Control: 5.2 ± 0.1 mm, n=17, P =0.002) and worse LV function (EF, CRP-Tg: 13 ± 2%, n=14; Control: 19 ± 1%, n=17, P =0.01). Hemodynamic studies indicated that LV +dP/dt (CRP-Tg: 2,947 ± 480 mmHg/s, n=9; Control: 3,788 ± 656 mmHg/s, n=10, P =0.02) and -dP/dt (CRP-Tg: −2,230 ± 48 mmHg/s, n=9; Control: −2,890 ± 161 mmHg/s, n=10, P =0.003) were lower in the CRP-Tg group than in the Control group, although infarct size was comparable. Histological evaluation at one week after MI showed a higher rate of apoptosis in the border zone of infarcted hearts from CRP-Tg mice (CRP-Tg: 1,434 ± 322 per 10 5 nuclei; Control: 596 ± 112 per 10 5 nuclei, n=6 for each, P =0.03). Quantitative RT-PCR showed that angiotensin II type 1a receptor and interleukin-6 were upregulated in viable LV samples from CRP-Tg mice compared with controls. Increased CRP expression exacerbates LV dysfunction and remodeling after MI, associated with increased apoptotic rates, increased angiotensin II receptor expression and exaggerated inflammatory response.

Biphasic temporal pattern in exercise capacity after myocardial infarction in the rat: relationship to left ventricular remodeling

2005 ◽  
Vol 288 (1) ◽  
pp. H244-H249 ◽  
Author(s):  
Nathan A. Trueblood ◽  
Patrick R. Inscore ◽  
Daniel Brenner ◽  
Daniel Lugassy ◽  
Carl S. Apstein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Exercise Capacity ◽  
Time Course ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Early Recovery ◽  
Functional Changes ◽  
Lv Remodeling

After myocardial infarction (MI), there is progressive left ventricular (LV) remodeling and impaired exercise capacity. We tested the hypothesis that LV remodeling results in structural and functional changes that determine exercise impairment post-MI. Rats underwent coronary artery ligation ( n = 12) or sham ( n = 11) surgery followed by serial exercise tests and echocardiography for 16 wk post-MI. LV pressure-volume relationships were determined using a blood-perfused Langendorff preparation. Exercise capacity was 60% of shams immediately post-MI ( P < 0.05) followed by a recovery to near normal during weeks 5– 8. Thereafter, there was a progressive decline in exercise capacity to ±40% of shams ( P < 0.01). At both 8 and 16 wk post-MI, fractional shortening (FS) was reduced and end-diastolic diameter (EDD) was increased ( P < 0.01). However, neither FS nor EDD correlated with exercise at 8 or 16 wk ( r2 < 0.12, P > 0.30). LV septal wall thickness was increased at both 8 ( P = 0.17 vs. shams) and 16 wk ( P = 0.035 vs. shams) post-MI and correlated with exercise at both times ( r2 ≥ 0.50 and P ≤ 0.02 at 8 and 16 wk). Neither end-diastolic volume nor maximum LV developed pressure at 16 wk correlated with exercise capacity. Exercise capacity follows a biphasic time course post-MI. An immediate decrease is followed by an early recovery phase that is associated with compensatory LV hypertrophy. Subsequently, there is a progressive decrease in exercise capacity that is independent of further changes in LV volume or contractile function.

scholarly journals Prognostic implications of left ventricular torsion by feature-tracking cardiac magnetic resonance in patients with ST-elevation myocardial infarction

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
LAI Wei ◽  
HENG Ge ◽  
JUN Pu
Keyword(s):  
Myocardial Infarction ◽  
Acute Phase ◽  
Risk Model ◽  
Left Ventricular ◽  
Independent Predictive Factor ◽  
Normal People ◽  
Lv Remodeling ◽  
St Elevation ◽  
Prognostic Implications ◽  
Lv Aneurysm

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China OnBehalf Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University Background  The prognostic implications of left ventricular (LV) torsion on the long-term prognosis of patients with acute ST-elevation myocardial infarction (STEMI) is not clear. Methods  We analyzed Cardiac Magnetic Resonance (CMR) images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12h and CMR examination within 1 week (median,5 days; range, 2-7 days) after infarction. Besides, CMR images of 40 normal people were enrolled as the control group. LV torsion, torsion rate and other conventional CMR indexes were measured. Ultrasound cardiogram examinations were performed in the acute phase and 1 year post-STEMI to assess LV remodeling (≥ 20% increase in LV end-diastolic volume). Primary end point was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. Secondary end points were the formation of LV aneurysm/thrombus in hospital as well as LV remodeling at 1 year post-STEMI. Results During follow-up (median: 52 months, inter-quartile range: 29–78 months), 80 patients developed MACCEs. Compared with normal people, patients with STEMI had more decreased LV torsion (P &lt; 0.001) and torsion rate (P = 0.033). Patients who experienced MACCEs had more impaired LV torsion (P &lt; 0.001) and torsion rate (P &lt; 0.001) than those who didn’t. LV torsion ≤ 0.876 deg/cm in the acute phase of STEMI was an independent predictive factor of MACCE (P = 0.001) and LV remodeling (P = 0.001). Patients with impaired LV torsion were more likely to experience MACCEs (P &lt; 0.001). The impairment of LV torsion was also associated with the higher incidence of LV aneurysm (P &lt; 0.001) and thrombus (P = 0.006). The addition of LV torsion to a risk model comprising LV ejection fraction (LVEF), infarct size (IS), and microvascular obstruction (MVO) led to a net reclassification improvement (continuous NRI 0.499 [95% CI, 0.261–0.737]; P &lt; 0.001). Hypertension (P = 0.047), tobacco use (P = 0.005), worse TIMI flow post-PCI (P &lt; 0.001), more extensive IS (P &lt; 0.001) / MVO size (P = 0.002) were associated with the impairment of LV torsion. Conclusions Compared with normal people, patients with STEMI had more decreased LV torsion and torsion rate. LV torsion ≤ 0.876 deg/cm in the acute phase was an independent predictive factor of MACCE and LV remodeling. The addition of LV torsion to a risk model comprising LVEF, LV-IS and LV-MVO significantly improved risk stratification of patients with STEMI .

Abstract 3809: Cardiac-Specific Overexpression of EcSOD Using an AAV9 Vector in Combination with the Cardiac Troponin-T Promoter Inhibits LV Remodeling after Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Konkal-Matt R Prasad ◽  
Ronald J Beyers ◽  
Yaqin Xu ◽  
Brent A French
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Left Ventricular ◽  
The Body ◽  
Cardiac Troponin T ◽  
Sod Activity ◽  
Western Blots ◽  
Systemic Injection ◽  
Lv Remodeling

Introduction: The wide tissue tropism exhibited by AAV provides for efficient gene transfer throughout the body, but targeting gene expression to cardiomyocytes is desirable for cardiac gene therapy. We hypothesized that targeted overexpression of extracellular superoxide dismutase (EcSOD) via the cardiac Troponin-T (cTnT) promoter would suffice to minimize left ventricular (LV) remodeling after myocardial infarction (MI). Methods: An AAV9 vector expressing EcSOD from the cTnT promoter (AcTnTEcSOD) was injected into 5 wk-old C57 mice via jugular vein (3x10 11 vp/mouse). Western blots, immunohistochemistry & in vitro SOD assays were used to measure EcSOD expression, distribution and activity. Cardiac magnetic resonance (CMR) imaging was performed at baseline (5 wks post-vector injection) and at days 1, 7 & 28 after MI to assess LV volumes (vol) & ejection fraction (EF) as compared to WT mice (n=4). Infarct (IF) sizes were also compared by DE on D1. Results: Systemic injection of the vector (AcTnTEcSOD) provided uniform EcSOD overexpression within cardiomyocytes (Panels A&B) and elevated total cardiac SOD activity by 5.6 fold (p<0.05). On D1 post-MI, IF sizes were similar in vector & WT groups (p=ns). The vector group had significantly lower end-diastolic vol at D7, D28 and lower end-systolic vol at D28 (all p<0.05 by ANOVA, Panels C&D), resulting in improved D28 EF over controls (p=0.02). Conclusions: Cardiac-specific overexpression of therapeutic genes can be achieved by combining highly-efficient AAV9 vectors with cardiac-specific promoters. AAV-mediated, cardiac-restricted overexpression of EcSOD from the cTnT promoter significantly reduces post-MI LV remodeling.

Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction

2010 ◽  
Vol 299 (6) ◽  
pp. H1795-H1804 ◽  
Author(s):  
Toshiyuki Takahashi ◽  
Toshihisa Anzai ◽  
Hidehiro Kaneko ◽  
Yoshinori Mano ◽  
Atsushi Anzai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Macrophage Infiltration ◽  
Border Zone ◽  
Histological Evaluation ◽  
Coronary Artery Ligation ◽  
Apparent Difference ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Lv Remodeling

We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.

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