Depletion of cardiac cardiolipin synthase alters systolic and diastolic function.
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ABSTRACT:
SUBMITTER: Smeir E
PROVIDER: S-EPMC8581512 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Depletion of cardiac cardiolipin synthase alters systolic and diastolic function.
Smeir Elia E Leberer Sarah S Blumrich Annelie A Vogler Georg G Vasiliades Anastasia A Dresen Sandra S Jaeger Carsten C Gloaguen Yoann Y Klose Christian C Beule Dieter D Schulze P Christian PC Bodmer Rolf R Foryst-Ludwig Anna A Kintscher Ulrich U
iScience 20211019 11
Cardiolipin (CL) is a major cardiac mitochondrial phospholipid maintaining regular mitochondrial morphology and function in cardiomyocytes. Cardiac CL production includes its biosynthesis and a CL remodeling process. Here we studied the impact of CL biosynthesis and the enzyme cardiolipin synthase (CLS) on cardiac function. CLS and cardiac CL species were significantly downregulated in cardiomyocytes following catecholamine-induced cardiac damage in mice, accompanied by increased oxygen consumpt ...[more]
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Project description:AimsBlood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data.MethodsIn this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals.ResultsAge and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002.ConclusionCMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters.
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Project description:ObjectiveThe influence of diabetes on cardiac resynchronization therapy (CRT) remains unclear. The aims of the current study were to 1) assess the changes in left ventricular (LV) systolic and diastolic function and 2) evaluate long-term prognosis in CRT recipients with diabetes.Research design and methodsA total of 710 CRT recipients (171 with diabetes) were included from an ongoing registry. Echocardiographic evaluation, including LV systolic and diastolic function assessment, was performed at baseline and 6-month follow-up. Response to CRT was defined as a reduction of ≥15% in LV end-systolic volume (LVESV) at the 6-month follow-up. During long-term follow-up (median = 38 months), all-cause mortality (primary end point) and cardiac death or heart failure hospitalization (secondary end point) were recorded.ResultsAt the 6-month follow-up, significant LV reverse remodeling was observed both in diabetic and non-diabetic patients. However, the response to CRT occurred more frequently in non-diabetic patients than in diabetic patients (57 vs. 45%, P < 0.05). Furthermore, a significant improvement in LV diastolic function was observed both in diabetic and non-diabetic patients, but was more pronounced in non-diabetic patients. The determinants of the response to CRT among diabetic patients were LV dyssynchrony, ischemic cardiomyopathy, and insulin use. Both primary and secondary end points were more frequent in diabetic patients (P < 0.001). Particularly, diabetes was independently associated with all-cause mortality together with ischemic cardiomyopathy, renal function, LVESV, LV dyssynchrony, and LV diastolic dysfunction.ConclusionsHeart failure patients with diabetes exhibit significant improvements in LV systolic and diastolic function after CRT, although they are less pronounced than in non-diabetic patients. Diabetes was independently associated with all-cause mortality.
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Project description:The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.
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Project description:BackgroundDiabetes mellitus (DM) increases risk of heart failure. It has been shown that diabetes leads to DM-cardiomyopathy, characterized by systolic and diastolic dysfunction. Pre-transplant diastolic dysfunction, has been associated with poor graft outcome and mortality. We assessed the hypothesis that end-stage liver disease (ESLD) patients with diabetes (DM-ESLD), have more advanced cardiac systolic and diastolic dysfunction, compared to ESLD patients without diabetes (Non DM-ESLD).MethodsWe retrospectively evaluated preoperative echocardiography of 1,319 consecutive liver transplant recipients (1,007 Non DM-ESLD vs. 312 DM-ESLD [23.7%]) January 2012-May 2016. Systolic and diastolic indices, such as left ventricular ejection fraction, transmital E/A ratio, tissue doppler s', e' velocity, and E/e' ratio (index of left ventricular end-diastolic pressure), were compared using 1:2 propensity-score matching.ResultsDM-ESLD patients showed no differences in systolic indices of left ventricular ejection fraction and s' velocity, whereas diastolic indices of E/A ratio ≤ 1 (49.0% vs. 40.2% P = 0.014), e' velocity (median = 7.0 vs. 7.4 cm/s, P < 0.001) and E/e' ratio (10.9 ± 3.2 vs. 10.1 ± 3.0, P < 0.001), showed worse diastolic function compare with Non DM-ESLD patients, respectively.ConclusionsDM-ESLD patients suffer higher degree of diastolic dysfunction compared with Non DM-ESLD patients. Based on this, careful preoperative screening for diastolic dysfunction in DM-ESLD patients is encouraged, because poor transplant outcomes have been noted in patients with preoperative diastolic dysfunction.
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Project description:Background and Objectives: No data are available on whether the heritability of left ventricle (LV) systolic and diastolic parameters are independent of each other. Therefore, our aim was to assess the magnitude of common and independent genetic and environmental factors defining LV systolic and diastolic function. Materials and Methods: We analyzed 184 asymptomatic twins (65% female, mean age: 56 ± 9 years). Transthoracic echocardiography was performed to measure LV systolic (global longitudinal and circumferential strain; basal and apical rotation) and diastolic (early diastolic velocity of mitral inflow and lateral mitral annulus tissue; deceleration time and early diastolic strain rate) parameters using conventional and speckle-tracking echocardiography. Genetic structural equation models were evaluated to quantify the proportion of common and specific genetic (Ac, As) and environmental factors (Ec, Es) contributing to the phenotypes. Results: LV systolic parameters had no common genetic or environmental heritability (Ac range: 0-0%; Ec range: 0-0%; As range: 57-77%; Es range: 24-43%). Diastolic LV parameters were mainly determined by common genetic and environmental effects (Ac range: 9-40%; Ec range: 11-49%; As range: 0-29%; Es range: 0-51%). Systolic parameters had no common genetic or environmental factors (Ac = 0%; Ec = 0%) with diastolic metrics. Conclusions: Systolic LV parameters have a strong genetic predisposition to any impact. They share no common genetic or environmental factors with each other or with diastolic parameters, indicating that they may deteriorate specifically to given effects. However, diastolic functional parameters are mainly affected by common environmental influences, suggesting that pathological conditions may deteriorate them equally. Estimation of the genetic and environmental influence and interdependence on systolic and diastolic LV function may help the understanding of the pathomechanism of different heart failure classification types.
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