Myocardial infarction causes rapid impairment of left ventricular function and requires a hypercontractile response of non-infarcted tissue areas to maintain haemodynamic stability. This compensatory adaptation is mediated by humoral, inflammatory and neuronal signals. GLP-1 is an incretin hormone with glucoregulatory and cardioprotective capacities and is secreted in response to nutritional and inflammatory stimuli. Inactivation of GLP-1 is caused by the ubiquitously present enzyme DPP-4. In this study, circulating concentrations of GLP-1 were assessed after myocardial infarction and were evaluated in the light of metabolism, left ventricular contractility and mitochondrial function. Circulating GLP-1 concentrations were markedly increased in patients with acute myocardial infarction. Experimental myocardial infarction by permanent LAD ligation proved sufficient to increase GLP-1 secretion in mice. This took place in a time-dependent manner, which coincided with the capacity of DPP-4 inhibition, by linagliptin, to augment left ventricular contractility in a GLP-1 receptor-dependent manner. Mechanistically, DPP-4 inhibition increased AMPK activity and stimulated the mitochondrial respiratory capacity of non-infarcted tissue areas. We describe a new functional relevance of inflammatory GLP-1 secretion for left ventricular contractility during myocardial infarction.
Aims: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1. Relevance of PYY in the context of cardiovascular disease has not been explored. In this study, we aimed to investigate PYY serum concentrations in patients with acute myocardial infarction and to evaluate their association with cardiovascular events. Material and Methods: PYY levels were assessed in 834 patients presenting with acute myocardial infarction (553 Non-ST-Elevation Myocardial Infarction (NSTEMI) and 281 ST-Elevation Myocardial Infarction (STEMI)) at the time of hospital admission. The composite outcomes of first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke (3-P-MACE), and all-cause mortality were assessed with a median follow-up of 338 days. Results: PYY levels were significantly associated with age and cardiovascular risk factors, including hypertension, diabetes, and kidney function in addition to biomarkers of heart failure (NT-pro BNP) and inflammation (hs-CRP). Further, PYY was significantly associated with 3-P-MACE (HR: 1.7; 95% CI: 1–2.97; p = 0.0495) and all-cause mortality (HR: 2.69; 95% CI: 1.61–4.47; p = 0.0001) by univariable Cox regression analyses, which was however lost after adjusting for multiple confounders. Conclusions: PYY levels are associated with parameters of cardiovascular risk as well as cardiovascular events and mortality in patients presenting with acute myocardial infarction. However, this significant association is lost after adjustment for further confounders.
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