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Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome.

ABSTRACT: Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß₁AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß₁AR-Ab levels at the time of ACS onset. Serum anti-ß₁AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß₁AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß₁AR Ab concentrations were associated with STEMI (p?=?0.001). Across all ACS patients, no associations between anti-ß₁AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p?=?0.14) were evident. However among STEMI patients ?60 years with anti-ß₁AR Ab concentration 1AR Ab concentrations?>?median (14/198 (7.1%) vs. 2/190 (1.1%)); p?=?0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p?=?0.017). ACS Patients ?60 years, exhibiting lower concentrations of ß₁AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß₁AR Ab levels should be considered.

SUBMITTER: Ernst D

PROVIDER: S-EPMC6787077 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome.

Ernst Diana D Westerbergh Johan J Sogkas Georgios G Jablonka Alexandra A Ahrenstorf Gerrit G Schmidt Reinhold Ernst RE Heidecke Harald H Wallentin Lars L Riemekasten Gabriela G Witte Torsten T

Scientific reports 20191010 1

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratifi ...[more]

PMID: 31601947

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Project description:BackgroundInhibition of proteolytic MMP activity could be a therapeutic approach to prevent ventricular dilatation by diminishing collagen matrix turnover and interstitial fibrosis. We investigated the time-course of MMP/TIMP activity during transition from hypertrophy to ventricular dilatation in transgenic mice with myocyte overexpression of the human beta1-adrenergic receptor (beta1TG). These beta1TG mice were studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular dilatation) months of age compared to age-matched controls (WT).MethodsPicro Sirius red staining and real-time PCR were performed for total collagen and for collagen type I and III quantification, respectively. MMP-activity assays (zymography), immunoblotting and real-time PCR experiments were done for gelatinase- (MMP-2, -9), collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14) and TIMP expression measurements. To investigate beta1-integrin activity, integrin-linked kinase (ILK) expression was measured by immunoblotting.ResultsCompared to WT with normal cardiac function, interstitial collagen type I and III mRNA and protein expression increased 3.6-fold in beta1TG at 5 months of age with moderate fibrosis and cardiomyocyte hypertrophy and 17-fold in beta1TG at 12 months of age with severe fibrosis and ventricular dilatation. Protein expression of the collagenases MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the beta1TG group with cardiac hypertrophy. Maximal activity of the gelatinase MMP-2 (3.5-fold vs.WT) was measured in beta1TG at 12 months of age with severe fibrosis and ventricular dilatation, accompanied by coexpression of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes.ConclusionThese data provide evidence that sympathetic overactivation can trigger interstitial matrix remodeling and fibrosis by induction of MMP/TIMP activity. In particular gelatinolytic MMP-2 activity accompanies ventricular dilatation and the development of heart failure.

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Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome.

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Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome.

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