Natural and synthetic peptides in the cardiovascular diseases: An update on diagnostic and therapeutic potentials

Grieco, Paolo; Gómez-Monterrey, Isabel

doi:10.1016/j.abb.2018.11.021

Cited by 29 publications

(16 citation statements)

References 270 publications

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“…The former is a biomarker that reflects myocardial stress and volume overload, is an established biomarker for the diagnosis of HF and for the prognosis of adverse outcomes . In CV disease, MR‐proADM secretion is related to vasoregulatory processes and local inflammation and elevated blood concentrations are associated with increased disease severity as assessed by NYHA class and left ventricular dysfunction . MR‐proADM has been shown to improve risk prognosis in patients with chronic HF if added to natriuretic peptides or clinical models .…”

Section: Discussionmentioning

confidence: 99%

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial

Möckel

Koehler

Anker

et al. 2019

European J of Heart Fail

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Aims The TIM‐HF2 study showed less days lost due to unplanned cardiovascular hospitalization or all‐cause death and improved survival in patients randomly assigned to remote patient management (RPM) instead of standard of care. Methods and results This substudy explored whether the biomarkers mid‐regional pro‐adrenomedullin (MR‐proADM) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) could be used to identify low‐risk patients unlikely to benefit from RPM, thereby allowing more efficient allocation of the intervention. For 1538 patients of the trial (median age 73 years, interquartile range 64–78 years, 30% female), baseline biomarkers were used to select subpopulations recommended for RPM with various safety endpoints (100%, 98%, 95% sensitivity), and efficacy of RPM was assessed. Both biomarkers were strongly associated with events. The primary endpoint of lost days increased from 1.0% (1.4%) in the lowest to 17.3% (17.6%) in the highest quintile of NT‐proBNP (MR‐proADM). After combining biomarkers to identify patients recommended for RPM with 95% sensitivity, in the most efficient scenario (excluding 27% of patients; NT‐proBNP < 413.7 pg/mL and MR‐proADM < 0.75 nmol/L), the effect of RPM on patients was highly similar to the original trial (ratio of lost days: 0.78, hazard ratio for all‐cause death: 0.68). Number needed to treat for all‐cause death was lowered from 28 to 21. Rates of emergencies and telemedical efforts were significantly lower among patients not recommended for RPM. Biomarker guidance would have saved about 150 h effort/year per 100 patients of the eligible population. Conclusions The combined use of MR‐proADM and NT‐proBNP may allow safe, more precise, effective and cost‐saving allocation of patients with heart failure to RPM and warrants further prospective studies.

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Section: Discussionmentioning

confidence: 99%

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial

Möckel

Koehler

Anker

et al. 2019

European J of Heart Fail

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“…First, we have not measured cardiac or systemic ANP or BNP levels. In this regard, increased levels of NPs have been reported in symptomatic HF subjects, and are considered an indication of myocardial response to hemodynamic alterations or impaired responsiveness to the effects of NP due to counter regulatory signaling pathways [77][78][79]. In contrast, NP levels are often lower in the setting of obesity due to either impaired NP production or its enhanced degradation [80,81].…”

Section: Discussionmentioning

confidence: 99%

Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness

Aroor

Mummidi

López-Alvarenga

et al. 2021

Cardiovasc Diabetol

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Objective Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy. Methods Sixteen-week-old male Zucker Obese rats (ZO; n = 64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg−1•day−1; ZOSV); Group 3: valsartan (31 mg•kg−1•day−1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg−1•day−1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage. Results Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val decreased aortic stiffness and reversed impairment in nitric oxide-induced vascular relaxation in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective than val in ameliorating DD. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, cytokine array revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val, suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val, but not val, increased IL-4, which is increasingly recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity-associated DD. Conclusions These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.

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“…Urotensin II (UII) is the most potent vasoactive substance [3] and its binding to the G protein-coupled receptor GPR14 (also named as UT) produces a variety of biological effects and is involved in multiple cardiovascular diseases, such as essential hypertension, coronary heart disease, congestive heart failure, diabetes mellitus and renal failure [3][4][5]. In addition, recent evidence suggested UII contributes to the development of atherosclerotic cardiovascular diseases [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Dynamic Changes in Plasma Urotensin II and Its Correlation With Plaque Stability

Yin

Wang

et al. 2021

Journal of Cardiovascular Pharmacology

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Background: Urotensin II (UII) is involved in the formation of atherosclerosis, but its role in the stability of atherosclerotic plaque is undetermined. The purpose of this study was to observe the dynamic change of plasma UII and analyze its relationship with the stability of atherosclerotic plaques. Methods: The plasma UII concentration in patients with acute coronary syndrome (ACS) was detected. A vulnerable plaque model was established by local transfection of a recombinant P53 adenovirus into plaques of rabbits fed with a high-cholesterol diet and subjected to balloon injury, to evaluate the stability of the atherosclerotic plaques.Results: Our results showed that the level of plasma UII was increased in ACS patients compared with healthy subjects. However, it was signi cantly decreased in ST-segment elevation myocardial infarction patients (STEMI) and increased again in acute myocardial infarction (AMI) patients that were discharged after three months. UII dynamic change and its correlation with plaques stabilities were further veri ed in rabbit with atherosclerotic vulnerable plaque. The UII level in rabbits was signi cantly decreased after P53 gene transfection which can lead to of plaque instability. Conclusions:In conclusion, the level of plasma UII was signi cantly decreased in ACS with STEMI, which may serve as a reliable biological marker to re ect the progression and stability of atherosclerotic plaques.

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Natural and synthetic peptides in the cardiovascular diseases: An update on diagnostic and therapeutic potentials

Cited by 29 publications

References 270 publications

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial

Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial

Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness

Dynamic Changes in Plasma Urotensin II and Its Correlation With Plaque Stability

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