Related Experiment Video
Updated: Aug 17, 2025
08:01
LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and Asparagine Deamidation in Shotgun Proteomics
Published on: April 9, 2017
8.2K
Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure
Kymberleigh A Romano1, Ina Nemet1, Prasenjit Prasad Saha1
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).
Circulation. Heart Failure
|December 16, 2022
Summary
The gut metabolite phenylacetylgutamine (PAGln) is linked to heart failure (HF) presence and severity. Targeting gut microbiome and PAGln production may offer new therapeutic strategies for HF.
Area of Science:
- Cardiovascular Research
- Microbiome Research
- Metabolomics
Background:
- Gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is associated with atherothrombotic heart disease.
- PAGln is mechanistically linked to cardiovascular disease via adrenergic receptor signaling.
Purpose of the Study:
- To investigate the clinical and mechanistic relationships between PAGln and heart failure (HF).
- To assess PAGln's impact on cardiovascular phenotypes relevant to HF.
Main Methods:
- Examined plasma PAGln levels and HF associations in two independent clinical cohorts (US and European).
- Assessed PAGln's effects on cardiomyoblasts and in vivo cardiovascular phenotypes.
- Utilized coronary angiography data, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide measurements.
Main Results:
- Circulating PAGln levels showed a dose-dependent association with HF presence and severity, independent of traditional risk factors and renal function.
- Mechanistic studies revealed PAGln and phenylacetylglycine induced HF-relevant phenotypes in vitro and in vivo.
- Observed decreased cardiomyocyte contraction and B-type natriuretic peptide gene expression.
Conclusions:
- The gut microbial metabolite PAGln is clinically and mechanistically linked to HF.
- Modulating the gut microbiome and PAGln production presents a potential therapeutic target for HF management.
Related Concept Videos
01:17Pathophysiology of Heart Failure
1.7K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.7K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
482
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
482
01:29Heart Failure II: Pathophysiology
23
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
23
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
138
Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
138
01:22Inorganic Nitrogen Assimilation
65
Nitrogen is an essential element in biological systems, forming a crucial component of proteins, nucleic acids, and other cellular constituents. Many bacteria and archaea acquire nitrogen in the form of nitrate (NO₃⁻) or ammonia (NH₃), which are then assimilated into biomolecules through specific enzymatic pathways.Assimilatory Nitrate ReductionWhen nitrate enters the cell, it undergoes a two-step reduction process known as assimilatory nitrate reduction. Initially, the enzyme...
65
01:30Heart Failure V: Medical Management
19
Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...
19