Emerging role of neurotensin in regulation of the cardiovascular system

Osadchii, Oleg E.

doi:10.1016/j.ejphar.2015.05.025

Cited by 47 publications

(41 citation statements)

References 115 publications

(222 reference statements)

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“…Neurotensin is believed to work as a local hormone on peripheral organs, including the heart; it has a broad range of cardiovascular effects, regulating heart rate, myocardial contractility, and blood pressure 6 . Though measurement of neurotensin had been challenging due to analytical instability, recent development of a pro-peptide assay to quantify neurotensin has overcome this challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotensin has a wide range of biologic roles in the body 5 , notably including a broad range of effects on the cardiovascular system; these include regulation of heart rate, myocardial contractility, as well as vascular tone 6 . Effects of neurotensin are transduced primarily through three receptors: the G-protein coupled NTS1 and NTS2 receptors and the non-G protein coupled NTS3, otherwise known as SORT1, a member of the Vps10p-domain receptor family.…”

mentioning

confidence: 99%

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Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

Januzzi

Lyass

Liu³

et al. 2016

ATVB

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Objective Neurotensin is a peptide whose receptor (SORT1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of pro-neurotensin (pro-NT; stable pro-fragment of neurotensin) would predict incident CV events in community-based subjects. Approach and Results Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for pro-NT. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and CV death); interaction between pro-NT concentration with sex, low density lipoprotein (LDL) concentrations or SORT1 single-nucleotide polymorphisms (SNP) was sought. At baseline, those in the highest log-pro-NT quartile were younger and heavier (P<0.001); across pro-NT quartiles, more prevalent hard CVD (from 3% to 7%; P<0.001) and diabetes mellitus (from 6% to 14; P<0.001) was present. In age and sex-adjusted models, log-pro-NT concentrations predicted incident hard CVD (hazard ratio [HR] = 1.24 per standard deviation [SD] change in log-pro-NT; 95% confidence intervals [CI] = 1.11–1.39; P<0.001), a finding that remained upon adjustment for standard CVD risk factors (HR 1.13; 95% CI = 1.01–1.27; P = 0.03). Elevated log-pro-NT concentrations were associated with shorter time to first event (P=0.02). We found no effect modification by sex, LDL concentration, or SORT1 SNPs. Concentrations of pro-NT were modestly associated with left ventricular mass and coronary artery calcium in these subjects. Conclusions Higher concentrations of pro-NT are associated with a greater risk of incident CV events in the community. This association did not vary according to sex, baseline LDL, or SORT1 genotype.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

Januzzi

Lyass

Liu³

et al. 2016

ATVB

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“…NT is a 13 amino acid peptide (Table 1) originally extracted from the bovine hypothalamus [110]. NT has been identified in all four chambers of the rat heart, with the left atrium having the greatest amount, followed by the right atrium, the right ventricle, and then the LV [111, 112].…”

Section: 0 Neurotensin (Nt)mentioning

confidence: 99%

“…There are three known NT receptors, NTS 1 , NTS 2 , and NTS 3 [110] (Table 1). NTS 1 and NTS 2 are 7 transmembrane spanning G-protein coupled receptors, with NTS 1 being the high affinity receptor and NTS 2 the low affinity receptor.…”

Section: 0 Neurotensin (Nt)mentioning

confidence: 99%

“…NTS 1 and NTS 2 are 7 transmembrane spanning G-protein coupled receptors, with NTS 1 being the high affinity receptor and NTS 2 the low affinity receptor. NTS 1 is expressed in rat cardiac tissue, while NTS 2 is expressed in rat and human, but not mouse cardiac tissue [110]. The NTS 3 receptor is an intracellular binding site expressed in human, rat, and mouse cardiac tissue, but not thought to mediate the major effects of NT on the heart.…”

Section: 0 Neurotensin (Nt)mentioning

confidence: 99%

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The role of neuropeptides in adverse myocardial remodeling and heart failure

Widiapradja

Chunduri

Levick

2017

Cell. Mol. Life Sci.

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In addition to traditional neurotransmitters of the sympathetic and parasympathetic nervous systems, the heart also contains numerous neuropeptides. These neuropeptides not only modulate the effects of neurotransmitters, but also have independent effects on cardiac function. While in most cases the physiological actions of these neuropeptides are well defined, their contributions to cardiac pathology are less appreciated. Some neuropeptides are cardioprotective, some promote adverse cardiac remodeling and heart failure, and in the case of others their functions are unclear. Some have both cardioprotective and adverse effects depending on the specific cardiac pathology and progression of that pathology. In this review, we briefly describe the actions of several neuropeptides on normal cardiac physiology, before describing in more detail their role in adverse cardiac remodeling and heart failure. It is our goal to bring more focus toward understanding the contribution of neuropeptides to the pathogenesis of heart failure, and to consider them as potential therapeutic targets.

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Bioactive Signaling in Next-Generation Pharmacotherapies for Heart Failure

et al. 2018

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Key PointsQuestionHas the time arrived for new heart failure therapeutic pathways over and above receptor antagonism to be considered?FindingsThis review identified that regulating angiotensin II receptor activation as well as activation of specific receptor pathways can provide favorable cardiovascular effects in the context of heart failure, which cannot be achieved by receptor inhibition alone.MeaningThe positive results of the PARADIGM-HF trial using a drug with both neutral endopeptidase and angiotensin II receptor inhibition properties heralds a shift in conventional concepts from solely using receptor inhibition in heart failure towards simultaneously potentiating novel signaling pathways.

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Emerging role of neurotensin in regulation of the cardiovascular system

Cited by 47 publications

References 115 publications

Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

The role of neuropeptides in adverse myocardial remodeling and heart failure

Bioactive Signaling in Next-Generation Pharmacotherapies for Heart Failure

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