ArticleHuman molecular genetics2013
MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- CircRNA-based AntimiR therapy: A novel approach to hypertension treatment.Non-coding RNA research · 2025Review
- Current perspectives and trends of the research on hypertensive nephropathy: a bibliometric analysis from 2000 to 2023.Renal failure · 2024Review
- MicroRNAs (miRNAs) role in hypertension: pathogenesis and promising therapeutics.Annals of medicine and surgery (2012) · 2024Review
- Chromogranin A and its derived peptides: potential regulators of cholesterol homeostasis.Cellular and molecular life sciences : CMLS · 2023Review
- Activation of Gαq sequesters specific transcripts into Ago2 particles.Scientific reports · 2022Article
- MicroRNAs in cardiovascular diseases.Medical review (2021) · 2022Review
- Benefits of Curcumin in the Vasculature: A Therapeutic Candidate for Vascular Remodeling in Arterial Hypertension and Pulmonary Arterial Hypertension?Frontiers in physiology · 2022Review
- MicroRNAs Regulating Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension.Biomolecules · 2021Review
- Differential Antihypertensive Effects of Oral Doses of Acetylcholine between Spontaneously Hypertensive Rats and Normotensive Rats.Foods (Basel, Switzerland) · 2021Article
- Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22.Pharmaceutical biology · 2020Article
- Can miRNAs Be Considered as Diagnostic and Therapeutic Molecules in Ischemic Stroke Pathogenesis?-Current Status.International journal of molecular sciences · 2020Review
- Chromogranin A pathway: from pathogenic molecule to renal disease.Journal of hypertension · 2020Article
- Nanoscale Technologies in Highly Sensitive Diagnosis of Cardiovascular Diseases.Frontiers in bioengineering and biotechnology · 2020Review
- Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology.Non-coding RNA · 2019Review
- Long-term high altitude hypoxia during gestation suppresses large conductance CaThe Journal of physiology · 2018Article
- Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity.International journal of molecular sciences · 2018Review
- Noncoding RNAs in the Regulatory Network of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Non-Coding RNA in the Pathogenesis, Progression and Treatment of Hypertension.International journal of molecular sciences · 2018Review
- MiR-664a-3p expression in patients with obstructive sleep apnea: A potential marker of atherosclerosis.Medicine · 2018Article
- Non-coding RNAs in cardiac hypertrophy.The Journal of physiology · 2017Review
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Authors and funding
21 authors at 8 institutions in 5 countries.
Funding
Abstract
Hypertension is a common hereditary syndrome with unclear pathogenesis. Chromogranin A (Chga), which catalyzes formation and cargo storage of regulated secretory granules in neuroendocrine cells, contributes to blood pressure homeostasis centrally and peripherally. Elevated Chga occurs in spontaneously hypertensive rat (SHR) adrenal glands and plasma, but central expression is unexplored. In this report, we measured SHR and Wistar-Kyoto rat (control) Chga expression in central and peripheral nervous systems, and found Chga protein to be decreased in the SHR brainstem, yet increased in the adrenal and the plasma. By re-sequencing, we systematically identified five promoter, two coding and one 3'-untranslated region (3'-UTR) polymorphism at the SHR (versus WKY or BN) Chga locus. Using HXB/BXH recombinant inbred (RI) strain linkage and correlations, we demonstrated genetic determination of Chga expression in SHR, including a cis-quantitative trait loci (QTLs) (i.e. at the Chga locus), and such expression influenced biochemical determinants of blood pressure, including a cascade of catecholamine biosynthetic enzymes, catecholamines themselves and steroids. Luciferase reporter assays demonstrated that the 3'-UTR polymorphism (which disrupts a microRNA miR-22 motif) and promoter polymorphisms altered gene expression consistent with the decline in SHR central Chga expression. Coding region polymorphisms did not account for changes in Chga expression or function. Thus, we hypothesized that the 3'-UTR and promoter mutations lead to dysregulation (diminution) of Chga in brainstem cardiovascular control nuclei, ultimately contributing to the pathogenesis of hypertension in SHR. Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (∼18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension.
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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.