ArticleHypertension (Dallas, Tex. : 1979)2012
Novel peptide isomer strategy for stable inhibition of catecholamine release: application to hypertension.
Article in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function.Communications biology · 2026Article
- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Oncogenesis · 2026Article
- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Research square · 2026Article
- The role of chromogranin A cleavage products in onset of type 1 and 2 diabetes.Frontiers in clinical diabetes and healthcare · 2026Review
- Catestatin suppresses melanoma progression and drug resistance through multitargeted modulation of signaling pathways.bioRxiv : the preprint server for biology · 2025Article
- Chromogranin A deficiency attenuates tauopathy by altering epinephrine-alpha-adrenergic receptor signaling in PS19 mice.Nature communications · 2025Article
- A complex role of chromogranin A and its peptides in inflammation, autoimmunity, and infections.Frontiers in immunology · 2025Review
- Catestatin: Antimicrobial Functions and Potential Therapeutics.Pharmaceutics · 2023Review
- Serum Catestatin Levels Correlate with Ambulatory Blood Pressure and Indices of Arterial Stiffness in Patients with Primary Hypertension.Biomolecules · 2022Article
- Putative regulation of macrophage-mediated inflammation by catestatin.Trends in immunology · 2022Review
- Gut microbial DNA and immune checkpoint gene Vsig4/CRIg are key antagonistic players in healthy aging and age-associated development of hypertension and diabetes.Frontiers in endocrinology · 2022Article
- Role of Catestatin in the Cardiovascular System and Metabolic Disorders.Frontiers in cardiovascular medicine · 2022Review
- Small Peptides for Inhibiting Serum Amyloid A Aggregation.ACS medicinal chemistry letters · 2021Article
- Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.Acta physiologica (Oxford, England) · 2021Article
- Immunosuppression of Macrophages Underlies the Cardioprotective Effects of CST (Catestatin).Hypertension (Dallas, Tex. : 1979) · 2021Article
- The associations between anxiety/depression and plasma chromogranin A among healthy workers: Results from EHOP study.Journal of occupational health · 2020Article
- Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation.Annals of the New York Academy of Sciences · 2019Review
- Catestatin as a Target for Treatment of Inflammatory Diseases.Frontiers in immunology · 2018Review
- Muscle injury, impaired muscle function and insulin resistance in Chromogranin A-knockout mice.The Journal of endocrinology · 2017Article
- Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity.Frontiers in endocrinology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although hypertension remains the most potent and widespread cardiovascular risk factor, its pharmacological treatment has achieved only limited success. The chromogranin A-derived fragment catestatin inhibits catecholamine release by acting as an endogenous nicotinic cholinergic antagonist and can rescue hypertension in the setting of chromogranin A-targeted ablation. Here, we undertook novel peptide chemistry to synthesize isomers of catestatin: normal/wild-type as well as a retro-inverso (R-I) version, with not only inversion of chirality (L → D amino acids) but also reversal of sequence (carboxyl → amino). The R-I peptide was entirely resistant to proteolytic digestion and displayed enhanced potency as well as preserved specificity of action toward nicotinic cholinergic events: catecholamine secretion, agonist desensitization, secretory protein transcription, and cationic signal transduction. Structural modeling suggested similar side-chain orientations of the wild-type and R-I isomers, whereas circular dichroism spectroscopy documented inversion of chirality. In vivo, the R-I peptide rescued hypertension in 2 mouse models of the human trait: monogenic chromogranin A-targeted ablation, with prolonged efficacy of the R-I version and a polygenic model, with magnified efficacy of the R-I version. These results may have general implications for generation of metabolically stable mimics of biologically active peptides for cardiovascular pathways. The findings also point the way toward a potential new class of drug therapeutics for an important risk trait and, more generally, open the door to broader applications of the R-I strategy in other pathways involved in cardiovascular biology, with the potential for synthesis of diagnostic and therapeutic probes for both physiology and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.