Neuropeptide Dynamics in Cardiovascular and Endocrine Systems

Neuropeptides constitute a diverse class of signalling molecules that arise from proteolytic processing of prohormones within neuroendocrine cells and act in autocrine, paracrine and endocrine modes. In the cardiovascular system, peptides such as catestatin, vasostatin and secretoneurin regulate vascular tone, cardiac contractility and endothelial barrier function through receptor-mediated pathways, intracellular calcium mobilisation and modulation of kinase cascades. In the endocrine realm, fragments derived from chromogranin A—including pancreastatin—influence insulin sensitivity, glucose homeostasis and lipid metabolism via interactions with intracellular signalling networks such as the phosphoinositide 3-kinase–Akt axis. Beyond direct vascular and metabolic control, many neuropeptides exert immunomodulatory actions by shifting macrophage polarisation or altering cytokine profiles, thereby linking cardiovascular health to systemic inflammation. The dynamic balance between opposing peptide fragments, determined by tissue-specific protease activity, is critical for maintaining homeostasis; dysregulation contributes to hypertension, heart failure, metabolic syndrome and pregnancy-related disorders. Emerging applications include the use of circulating neuropeptide levels as prognostic biomarkers and the development of peptide-based therapies or inhibitors to restore physiological equilibrium.

Research from Nature Portfolio

Investigation of a novel inhibitor of pancreastatin has demonstrated the potential to reverse insulin resistance in cellular and rodent models of type 2 diabetes. The peptide-based antagonist rescues glucose uptake by promoting GLUT4 translocation, enhances hepatic glycogenesis and diminishes gluconeogenesis via activation of the IRS1-PI3K-Akt-FoxO1 pathway, yielding improvements in glucose homeostasis comparable to established antidiabetic agents.

Work on catestatin in the context of cardiac ischaemia–reperfusion injury has revealed that this peptide binds selectively to type 2 muscarinic acetylcholine receptors on cardiomyocytes, triggering ERK1/2 and PI3K–Akt signalling. This activation curbs endoplasmic reticulum stress-induced apoptosis and mitigates myocardial damage, highlighting a cardioprotective mechanism distinct from its classical role in catecholamine modulation.

Neuropeptide Dynamics in Cardiovascular and Endocrine Systems publication trend

The graph below shows the total number of articles in neuropeptide dynamics in cardiovascular and endocrine systems across all publications each year (not limited to Nature Index journals).

Technical terms

Neuropeptide: A small protein or peptide produced by neuroendocrine cells that acts as a signalling molecule in the nervous, cardiovascular and endocrine systems.

Chromogranin A (CgA): A prohormone stored in secretory granules of neuroendocrine cells; its proteolytic fragments yield bioactive peptides with diverse physiological functions.

Catestatin: A 21-amino-acid peptide derived from CgA that modulates catecholamine release, vascular tone and immune cell function.

Pancreastatin: A CgA-derived peptide that negatively regulates insulin signalling and glucose metabolism, often elevated in insulin-resistant states.

Secretoneurin: A neuropeptide fragment of secretogranin II involved in angiogenesis, cardiomyocyte survival and endothelial function, with emerging utility as a biomarker in heart failure.

Proteolytic Processing: The enzymatic cleavage of precursor proteins into active peptides, a critical determinant of neuropeptide diversity and function.

References

1. The Role of Catestatin in Preeclampsia. International Journal of Molecular Sciences (2024).
2. Low catestatin as a risk factor for cardiovascular disease – assessment in patients with adrenal incidentalomas. Frontiers in Endocrinology (2023).
3. Prognostic value of plasma secretoneurin concentration in patients with heart failure with reduced ejection fraction in one-year follow-up. Annals of Medicine (2024).
4. Discovery of pancreastatin inhibitor PSTi8 for the treatment of insulin resistance and diabetes: studies in rodent models of diabetes mellitus. Scientific Reports (2018).
5. Catestatin attenuates endoplasmic reticulum induced cell apoptosis by activation type 2 muscarinic acetylcholine receptor in cardiac ischemia/reperfusion. Scientific Reports (2015).