scholarly journals XPO1 gene therapy restores cardiac function in rats with chronic induced myocardial infarction

2019 ◽  
Author(s):  
María García-Manzanares ◽  
Carolina Gil-Cayuela ◽  
Luis Martínez-Dolz ◽  
José Ramón González-Juanatey ◽  
Francisca Lago ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Human Heart Failure ◽  
Cytoplasmic Transport

AbstractBackgroundIn previous studies, we showed that several nuclear-cytoplasmic transport molecules were closely related to ventricular dysfunction in human heart failure. Particularly, the transcriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in heart failure patients of ischemic etiology. Therefore, we hypothesized that in a rat model of myocardial infarction treated with AAV9-shXPO1, an improvement in the ventricular function after a follow-up period may be observed.MethodsWe induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n=10), five of them received AAV9-shXPO1 treatment after four months and the other five infarcted rats did not receive any treatment. For non-failing controls, healthy Sham rats (n=5) received the placebo AAV9-scramble. Serial echocardiographic assessment was performed before, as well as, two and five months after intravenous injection.ResultsAAV9-shXPO1-treated rats showed improved fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P<0.05) and LV systolic (5.10 ± 0.79 vs 3.52 ± 0.88mm, P<0.05) and diastolic (6.17 ± 0.95 vs 4.70 ± 0.93mm, P<0.05) diameters when comparing measurements obtained before and five months after AAV9 injection. We did not observe this improvement in untreated infarcted rats. Furthermore, EXP-1 levels in rats heart, brain, skeletal muscle, and liver were determined by western-blot and compared to controls in AAV9-shXPO1-treated rats. Lower levels of EXP-1 in cardiac tissue were observed (P<0.05).DiscussionAt five months follow-up, ischemic AAV9-shXPO1-treated rats showed partial recovery of LV myocardial function. No secondary symptoms attributable to AAV9-shXPO1 were observed in skeletal muscle, liver and brain.

scholarly journals ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 396
Author(s):  
Wolf-Stephan Rudi ◽  
Michael Molitor ◽  
Venkata Garlapati ◽  
Stefanie Finger ◽  
Johannes Wild ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bone Marrow ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Vascular Inflammation ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin−Sca1−c-Kit+CD34+CD16/32+ granulocyte–macrophage progenitors (GMP) and Lin−Sca1−c-Kit+CD150−CD48− multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

Abstract 18973: Left Ventricular Function Improvement After Recent MI in Patients Using a Wearable Cardioverter Defibrillator

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Chingping Wan ◽  
Steven J Szymkiewicz
Keyword(s):  
Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Clinical Characteristics ◽  
Treated Group ◽  
Left Ventricular ◽  
Icd Implantation ◽  
Cardioverter Defibrillator ◽  
Wearable Cardioverter Defibrillator

Introduction: The wearable cardioverter defibrillator (WCD) has been used to protect AMI patients with reduced LVEF (≤35%) until ICD evaluation is recommended. The rate of EF improvement (e.g. EF>35%) over the initial 8-12 weeks after AMI has not been reported. METHODS: The manufacturer-maintained registry was searched for AMI patients who received a WCD shock for VT/VF between 05/2008 and 02/2013. The treated group was matched (1: ~4) with event-free WCD patients by ICD-9 code (410.*), gender, age and prescription date. Chart notes were reviewed for clinical characteristics. Follow-up was assessed through the registry and Social Security Death Master File. RESULTS: There were 992 (age=63±12, female=20.2%) AMI patients included in the final analysis, 206 treated by WCD and 786 event-free patients. Median follow-up was 334 days. Mean length of WCD use was 67±506 (median=38) days. Subgroup clinical characteristics are presented in Table 1. In the event-free group, 289 (38.9%) patients showed EF improvement to >35%. Nine (4.5%) in the treated group continued wearing the WCD until EF recovery, while 125 (60.7%) received ICD. Absence of recorded heart failure and/or diabetes were associated with LVEF recovery (p<.0001). CONCLUSION: In our study, almost 40% of AMI patients with initial EF ≤35% had EF improvement in two months. The EF recovery group had lower rates of heart failure and diabetes. WCD allows time for left ventricular function recovery in low EF post MI patients, optimizing ICD implantation decisions.

scholarly journals Epidemiology of Heart Failure Stages in Middle‐Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study

2021 ◽  
Author(s):  
Ramachandran S. Vasan ◽  
Solomon K. Musani ◽  
Kunihiro Matsushita ◽  
Walter Beard ◽  
Olushola B. Obafemi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Left Ventricular ◽  
Study Cohort ◽  
Atherosclerosis Risk In Communities ◽  
Cardiovascular Morbidity And Mortality ◽  
Atherosclerosis Risk

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993–1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0 : no risk factors; (2) Stage A : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D : prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all‐cause mortality on follow‐up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow‐up (median 19.0 years), 309 participants developed overt HF, 390 incurred new‐onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person‐years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5‐ to 2‐fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community‐based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

1997 ◽  
Vol 83 (4) ◽  
pp. 1291-1299 ◽  
Author(s):  
Michael D. Delp ◽  
Changping Duan ◽  
John P. Mattson ◽  
Timothy I. Musch
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Enzyme Activities ◽  
Fiber Type ◽  
Left Ventricular ◽  
Type I ◽  
Fiber Composition ◽  
Muscle Biochemistry ◽  
Type I Fibers

Delp, Michael D., Changping Duan, John P. Mattson, and Timothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure. J. Appl. Physiol. 83(4): 1291–1299, 1997.—One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls ( n = 13) and rats with moderate ( n = 10) and severe ( n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations ( P < 0.05) in left ventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD, 11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and β-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus

2020 ◽  
Author(s):  
Mei-Zhen Wu ◽  
Yan Chen ◽  
Yu-Juan Yu ◽  
Zhe Zhen ◽  
Ying-Xian Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Specific Pattern

Abstract Aims  Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. Methods and results  A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06–37.54; P &lt; 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67–7.89; P = 0.19). Conclusion  LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

Can left ventricular global function index be a novel marker of unfavorable outcome in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Minushkina ◽  
V Brazhnik ◽  
N Selezneva ◽  
V Safarjan ◽  
M Alekhin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Coronary Syndrome ◽  
Left Ventricular ◽  
Global Function ◽  
Coronary Syndrome ◽  
History Of ◽  
Coronary Events

Abstract   Left ventricular (LV) global function index (LVGFI) is a MRI marker of left ventricular remodeling. LVGFI has high predictive significance in young healthy individuals. The aim of the study was to assess prognostic significance in patients with acute coronary syndrome (ACS). We include into this analysis 2169 patients with ACS (1340 (61.8%) men and 829 (38.2%) women), mean age 64.08±12.601 years. All patients were observed in 2 Russian multicenter observational studies: ORACLE I (ObseRvation after Acute Coronary syndrome for deveLopment of trEatment options) (2004–2007 years) and ORACLE II (NCT04068909) (2014–2019 years). 1886 (87.0%) pts had arterial hypertension, 1539 (71.0%) – history of coronary artery disease, 647 (29.8%) – history of myocardial infarction, 444 (20.5%) - diabetes mellitus. Duration of the follow-up was 1 years after the hospital discharge. Cases of death from any cause, coronary deaths, repeated coronary events (fatal and non-fatal) were recorded. An echocardiographic study was conducted 5–7 days from the time of hospitalization. The LVGFI was defined as LV stroke volume/LV global volume × 100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). During the follow-up, 193 deaths were recorded (8.9%), 122 deaths (5.6%) were coronary. In total, repeated coronary events were recorded in 253 (11.7%) patients. Mean LVGFI was 22.64±8.121%. Patients who died during the follow-up were older (73.03±10.936 years and 63.15±12.429 years, p=0.001), had a higher blood glucose level at the admission to the hospital (8.12±3.887 mmol/L and 7.17±3.355 mmol/L, p=0.041), serum creatinine (110.86±53.954 μmol/L and 99.25±30.273 μmol/L, p=0.007), maximum systolic blood pressure (196.3±25.17 mm Hg and 190.3±27.83 mm Hg, p=0.042). Those who died had a lower LVGFI value (19.75±6.77% and 23.01±8.243%, p&lt;0.001). Myocardial mass index, ejection fraction and other left ventricular parameters did not significantly differ between died and alive patients. Among the patients who died, there were higher rate of women, pts with a history of myocardial infarction, heart failure, diabetes. In a multivariate analysis, diabetes mellitus OR1.67 95% CI [1.12–2.51] p=0.012, history of heart failure (1.78 [1.2.-2.59], p=0.003), a history of myocardial infarction (1.47 [1.05–2.05], p=0024), age (1.06 [1.05–1.08], p=0.001) and LVGFI &lt;22% (1.53 [1.08–2.17], p=0.015) were independent predictors of death from any cause. The LVGFI was also independently associated with the risk of coronary death, but not with the risk of all recurring coronary events. Thus, LVGFI may be useful the marker to assess risk in patients who have experienced an ACS episode. Funding Acknowledgement Type of funding source: None

scholarly journals Efficacy and Safety of PARACHUTE® Device: systematic review

2018 ◽  
Vol 64 (9) ◽  
pp. 853-860 ◽  
Author(s):  
Roberta da Silva Teixeira ◽  
Bruna Medeiros Gonçalves de Veras ◽  
Kátia Marie Simões e Senna ◽  
Rosângela Caetano
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Systematic Review ◽  
Left Ventricular ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Frequent Event

SUMMARY INTRODUCTION Heart failure due to an acute myocardial infarction is a very frequent event, with a tendency to increase according to improvements in the treatment of acute conditions which have led to larger numbers of infarction survivors. OBJECTIVE The aim of this study is to synthesize the evidence, through a systematic review, on efficacy and safety of the device in patients with this basic condition. METHODS Studies published between January 2002 and October 2016 were analysed, having as reference databases Embase, Medline, Cochrane Library, Lilacs, Web of Science and Scopus. The selection of studies, data extraction and methodological quality assessment of studies were examined by two independent reviewers, with disagreements resolved by consensus. RESULTS Only prospective studies without control group were identified. Six studies were included, with averages of 34 participants and follow-up of 13 months. Clinical, functional, hemodynamic and quality of life outcomes were evaluated. The highest mortality rate was 8.4% with 12-month follow-up for unspecified cardiovascular reasons, and heart failure rehospitalization was 29.4% with 36-month follow-up. Statistically significant improvements were found only in some of the studies which evaluating changes in left ventricular volume indices, the distance measured by the six-minute walk test, New York Heart Association functional classification, and quality of life, in pre and post-procedure analysis. CONCLUSIONS The present review indicates that no available quality evidence can assert efficacy and safety of PARACHUTE® in the treatment of heart failure after apical or anterior wall myocardial infarction.

scholarly journals One-Year Follow-up of Intracoronary Stem Cell Delivery on Left Ventricular Function Following ST-Elevation Myocardial Infarction

JAMA ◽  
2014 ◽  
Vol 311 (3) ◽  
pp. 301 ◽  
Author(s):  
Jay H. Traverse ◽  
Timothy D. Henry ◽  
Carl J. Pepine ◽  
James T. Willerson ◽  
Stephen G. Ellis
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Cell Delivery ◽  
Stem Cell Delivery ◽  
St Elevation ◽  
One Year

scholarly journals XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction

2019 ◽  
Vol 13 (4) ◽  
pp. 593-600
Author(s):  
María García-Manzanares ◽  
Estefanía Tarazón ◽  
Ana Ortega ◽  
Carolina Gil-Cayuela ◽  
Luis Martínez-Dolz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Dysfunction ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Coronary Ligation ◽  
Transcriptomic Signature ◽  
Echocardiographic Assessment

AbstractTranscriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in ischemic cardiomyopathy patients. We hypothesized that treatment with AAV9-shXPO1 attenuates left ventricular dysfunction and remodeling in a myocardial infarction rat model. We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n = 10), which received AAV9-shXPO1 (n = 5) or placebo AAV9-scramble (n = 5) treatment. Serial echocardiographic assessment was performed throughout the study. After myocardial infarction, AAV9-shXPO1-treated rats showed partial recovery of left ventricular fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P < 0.05) and a maintained left ventricular dimension (6.17 ± 0.95 vs 4.70 ± 0.93 mm, P < 0.05), which was not observed in non-treated rats. Furthermore, lower levels of EXP-1 (P < 0.05) and lower collagen fibers and fibrosis in cardiac tissue were observed. However, no differences were found in the IL-6 or TNFR1 plasma levels of the myocardium of AAV9-shXPO1 rats. AAV9-shXPO1 administration attenuates cardiac dysfunction and remodeling in rats after myocardial infarction, producing the gene silencing of XPO1.

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