Dipeptidyl peptidase IV and Mortality After an Acute Heart Failure Episode

Lourenço, Patrícia; Friões, Fernando; Silva, Nuno; Guimarães, João Tiago; Bettencourt, Paulo

doi:10.1097/fjc.0b013e3182949673

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…33,34 We found that the decline in the casual GLP-1 level contributes to the increased cardiac apoptosis in TAC/CON by demonstrating not only the effects of DPP4i but also those GLP-1 antagonist in vivo (Figures 3 and 4). One of the possible explanations for the pathological decline in the GLP-1 level can be found in the previous evidences demonstrating that circulating DPP4 activity is augmented in nondiabetic HF 4,5,35 because the DPP4 protease specifically truncates GLP-1. Akiyama et al 36 reported that the casual GLP-1 levels were reduced in patients with coronary artery disease, consistently suggesting the neurohormonal significance of the circulating GLP-1 in cardiovascular protection.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis

Aoyama

Kawase

Bando

et al. 2016

Circ: Heart Failure

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This study was conducted to address the essential effect of the DPP4i on myocardium in terms of cardiac function and remodeling using nondiabetic mice with pressure overload (thoracic aortic constriction [TAC]). We unexpectedly found the pathological decline in casual GLP-1 level with concomitant reduction of its second messenger cyclic AMP (cAMP) concentration in myocardium of TAC, which was prevented by ALO. In the context of exploring the molecular mechanism(s) underlying the GLP-1/cAMP pathway, we found that the GLP-1-induced cAMP elevation diversely signals not only protein kinase A (PKA) but also exchange protein directly activated by cAMP 1 (EPAC1). Furthermore, we found that

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Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis

Aoyama

Kawase

Bando

et al. 2016

Circ: Heart Failure

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“…Increased levels of DPPIV have been associated with poor outcomes in HF animals and patients (13,26,46). Several mechanisms may be responsible for this poor prognosis because several cardioprotective peptides are inactivated by DP-PIV.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, genetic deletion or pharmacological inhibition of DPPIV improves cardiovascular outcomes after myocardial infarction in both normoglycemic and diabetic mice (42). In addition, increased DPPIV activity in the plasma significantly correlates with poorer prognosis, including cardiac dysfunction and mortality in patients with heart failure (HF) (13,26,46).…”

Section: This Study Shows That Dipeptidyl Peptidase IV (Dppiv) Inhibimentioning

confidence: 99%

The contributions of dipeptidyl peptidase IV to inflammation in heart failure

Salles

Zogbi

Lima

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-α, IL-1β, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.

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“…The studies have looked at short term (48-72 hours) and intermediate term (4 weeks) infusions of native GLP-1 (7-36) amide. In conscious, chronically instrumented dogs, GLP-1 infusions (1.5pmol.kg.min) attenuated post ischemic contractile dysfunction after brief periods of myocardial ischemia [6,7]. In the same study, GLP-1 administration hastened the recovery of regional wall motion abnormalities and impaired isovolumic relaxation compared to control.…”

Section: Robust Pre-clinical Datamentioning

confidence: 76%

Metabolic Modulation with Incretins: Is the Bloom off the Rose?

Patterson¹

2017

J Cardiovasc Disord

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For the better part of a half century, cardiovascular physiologists have recognized that the failing heart is characterized by perturbations in myocardial metabolism whether or not heart failure is accompanied by myocardial ischemia. These metabolic derangements have long been a target of therapeutic intervention but with little or no evidence of therapeutic benefit. Attempts to drive substrate uptake, oxidation, or utilization have all proven ineffective in altering the natural history and clinical symptoms in heart failure. The shift in substrate preference from fatty acid to glucose oxidation as a means to achieve oxidative efficiency has led to a focus on driving glucose metabolism. Early efforts to employ supplemental insulin, glucose and potassium (GIK) inadvertently exacerbated heart failure due to the volume requirements. These early failure led to a consideration of agents which further impair fatty acid oxidation as an intrinsic means of driving glucose utilization but to no avail. Thus, the emergence of incretin based therapies as an intrinsic insulin dependent means to increase glucose uptake and disposal were heralded as a next generation of metabolic adjuvants. There emergence on the scene corresponded to a period in which modifying cardiovascular outcomes in diabetes has become an equally compelling clinical objective particularly given the occurrence of diabetes and heart failure in the world's population. Here we review what has been learned regarding the cardiovascular effects of incretin based therapies and their impact on the progression of heart failure. At this point, effective metabolic modulation with incretins in heart failure remains elusive.Keywords: Heart Failure; Myocardial Metabolism; Incretins; GlucagonLike-Peptide-1; Metabolites advanced heart failure have been plagued by the requirements of simultaneous infusion of dextrose to avoid hypoglycemia, further exacerbating underlying volume overload [4,5]. Thus, the promissory note remains unfulfilled with respect to metabolic modulation in heart failure as a new therapeutic approach. The Allure of Incretin Based TherapyFor these reasons, there was a great deal of enthusiasm when incretin therapies emerged as an effective treatment for Type 2 diabetes. Glucagon-Like Peptide-1 (GLP-1 7-36 amide)is a naturally occurring incretin peptide released from intestinal L cells that enhances cellular glucose uptake by stimulating insulin secretion. The insulin stimulating actions of GLP-1 cease at glucose levels below 4 mmol/L, mitigating the risk of hypoglycemia and the need for dextrose infusion. GLP-1 also promotes increased glucose uptake in target tissues via mechanisms independent of insulin action. GLP-1 receptors have been identified in myocardium and in vascular and endocardial endothelium making GLP-1 administration a putative pharmacologic intervention in heart failure and ischemic heart disease as a means to favorably influence myocardial metabolism.Native GLP-1 (7-36) amide requires continuous infusion due to rapid hydrolysis...

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Dipeptidyl peptidase IV and Mortality After an Acute Heart Failure Episode

Abstract: Discharge DPP IV ≥ 348.6 ng/mL conferred an approximately 3-fold higher risk of 6-month HF death. Further studies would be important to understand the role of DPP IV in HF.

Cited by 15 publications

References 31 publications

Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis

Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis

The contributions of dipeptidyl peptidase IV to inflammation in heart failure

Metabolic Modulation with Incretins: Is the Bloom off the Rose?

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