Prazosin in Chronic Congestive Heart Failure Due to Ischemic Heart Disease

Antani, J. A.; Antani, N.J.; Nanivadekar, A. S.

doi:10.1002/clc.4960140608

Cited by 10 publications

(6 citation statements)

References 11 publications

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“…The protein NQO2 was associated with a decreased risk of HF, through the amino acid breakdown product indoleacetylglutamine. Prazosin, which acts as an adrenergic receptor alpha-1 antagonist and targets NQO2, has shown potential benefits for HF patients in previous observational studies and trials (40,41), suggesting prazosin might be a relevant repurposing candidate for HF.…”

Section: Discussionmentioning

confidence: 99%

Integrating urinary and plasma omics to identify markers and therapeutic targets for cardiac disease

de Ruiter,

van Vugt,

Finan

et al. 2024

Preprint

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Introduction: Urinary metabolites, representing kidney regulated filtration of metabolism end products, contain cardiac disease biomarkers such as NT-proBNP. We set out to integrate plasma proteins with urinary metabolites to identify potentially druggable metabolic pathways for cardiac disease. Methods: Data was leveraged from a genome-wide association study (GWAS) on 954 urinary metabolites. Mendelian randomisation was used to identify urinary metabolites associating with atrial fibrillation (AF), heart failure (HF), dilated cardiomyopathy (DCM), or hypertrophic cardiomyopathy (HCM). By interrogating eight independent plasma protein GWAS, jointly including 92,277 participants and 1,562 unique proteins, we identified druggable plasma proteins with a directionally concordant effect on urinary metabolites and cardiac outcomes. Results: In total, 38 unique urinary metabolites associated with cardiac disease, predominantly covering breakdown products from amino acid metabolism (n=12), xenobiotic metabolism (n=5), and unclassified metabolism origins (n=16). Subsequently, we identified 32 druggable proteins expressed in cardiac tissue, which had a directionally concordant association with the identified urinary metabolites and cardiac outcomes. This included positive control findings, for example higher values of AT1B2 (targeted by digoxin) decreased the risk of HCM, which we were able to link to a novel unclassified urinary metabolite (X-15497). Additionally, we showed that increased plasma RET values, a mediator of GDF-15 signalling, reduced the risk of HF, and linked this to the novel unclassified urinary breakdown product X-23776. Conclusion: We were able to identify 32 druggable proteins affecting cardiac disease, and link these to urinary measurements of metabolite breakdown processes identifying potentially novel disease pathways.

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Section: Discussionmentioning

confidence: 99%

Integrating urinary and plasma omics to identify markers and therapeutic targets for cardiac disease

de Ruiter,

van Vugt,

Finan

et al. 2024

Preprint

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show abstract

“…Importantly, several clinical investigations have revealed the advantageous effects of α 1 -AR antagonists including prazosin in failing hearts due to different etiologies [ 90 , 91 , 92 , 93 ]. It should be mentioned that while co-administration of prazosin and metoprolol in heart failure was observed not to exert any additive effects [ 94 ], the results of the COMET trial (Carvedilol or Metoprolol European Trial), revealed a greater benefit of carvedilol in heart failure than with metoprolol alone [ 95 ].…”

Section: Evidence For Regression Of Abnormal Cardiomyocyte Growth By ...mentioning

confidence: 99%

Upregulation of Phospholipase C Gene Expression Due to Norepinephrine-Induced Hypertrophic Response

Tappia

Dhalla

2022

Cells

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The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte response to several different hypertrophic agents such as norepinephrine, angiotensin II and endothelin-1. PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream signal transducers for the expression of fetal genes, increased protein synthesis, and subsequent cardiomyocyte growth. In this article, we describe the signal transduction elements that regulate PLC gene expression. The discussion is focused on the norepinephrine- α1-adrenoceptor signaling pathway and downstream signaling processes that mediate an upregulation of PLC isozyme gene expression. Evidence is also indicated to demonstrate that PLC activities self-regulate the expression of PLC isozymes with the suggestion that PLC activities may be part of a coordinated signaling process for the perpetuation of cardiac hypertrophy. Accordingly, from the information provided, it is plausible that specific PLC isozymes could be targeted for the mitigation of cardiac hypertrophy.

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“…The efficiency of Terminalia arjuna therapy in ischemic stroke and ischemic heart diseases has been studied by several groups of researchers. In a study, 20g bark stem powder was administered in three divided doses to patients of angina and thrombotic stroke [88]. Functional improvement in motor power along with an increase in prothrombin time was noted in these cases.…”

Section: Anti-ischemic Activitiesmentioning

confidence: 99%

Terminalia arjuna: A Potential Ayurvedic Cardio Tonic

Thakur¹,

Kaurav²,

Chaudhary³

2021

Int. j. res. appl. sci. biotechnol.

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Herbal plants have been a significant source of therapeutic agents to cure human diseases. Plants are being in use for treating various kinds of diseases across the world. Terminalia arjuna is a widely used herbal plant since ancient times. The ancient indian practitioners utilized the powdered tree bark of arjuna for the treatment of "hritshool" (angina) and other cardiovascular problems. Terminalia arjuna is regionally called as arjuna which belongs to the combretaceae family. The plant is utilized as a medicine in the various indigenous system like ayurveda, siddha and unani. Arjunic acid, arjunolic acid, arjungenin, arjunone, arjunolone and luteolin, gallic acid, ellagic acid, oligomeric proanthocyanidins (opcs), phytosterols are the major phytoconstituents of Terminalia arjuna that possesses many useful biological properties like anti-microbial, anti-inflammatory, antioxidant, antifeedant, cardio protective, etc. Various clinical evidence of Terminalia arjuna and its beneficial effects on the cardiovascular system. The present review is summarizing the phytomedicinal value of Terminalia arjuna in ayurveda and the folk system of medicine.

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Prazosin in Chronic Congestive Heart Failure Due to Ischemic Heart Disease

Cited by 10 publications

References 11 publications

Integrating urinary and plasma omics to identify markers and therapeutic targets for cardiac disease

Integrating urinary and plasma omics to identify markers and therapeutic targets for cardiac disease

Upregulation of Phospholipase C Gene Expression Due to Norepinephrine-Induced Hypertrophic Response

Terminalia arjuna: A Potential Ayurvedic Cardio Tonic

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