Related Experiment Video

Updated: Jul 10, 2026

The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension
05:57

The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension

Published on: May 17, 2024

Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling

Utpal Sen1, Markus Herrmann, Wolfgang Herrmann

  • 1Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Clinical Chemistry and Laboratory Medicine
|November 10, 2007
PubMed

Insights

High homocysteine (HHcy) activates the angiotensin II type 1 (AT1) receptor, leading to vascular remodeling via ERK/STAT3 pathways. This study clarifies HHcy

Area of Science:

  • Cardiovascular Disease Research
  • Molecular Biology
  • Endothelial Cell Signaling

Background:

  • Hyperhomocysteinemia (HHcy) is a known cardiovascular disease risk factor.
  • Extracellular signal-regulated kinase-1/2 (ERK-1/2) and signal transducer and activator of transcription 3 (STAT3) pathways are implicated in matrix remodeling.
  • The role of these pathways in HHcy-mediated matrix metalloproteinase-9 (MMP-9) induction and vascular pathologies, particularly concerning the renin-angiotensin system, remains unclear.

Purpose of the Study:

  • To investigate the hypothesis that homocysteine (Hcy) activates the angiotensin II type 1 (AT1) receptor, potentiating STAT3 via ERK-1/2 phosphorylation.
  • To elucidate the role of Hcy-induced AT1 receptor activation in modulating MMP-9 and collagen, leading to vascular remodeling.

Main Methods:

  • Mouse aortic endothelial cells (MAEC) were exposed to varying concentrations and durations of Hcy.
  • Levels of AT1 receptor, ERK-1/2, STAT3, MMP-9, and collagen type-1 were quantified using immunoblot analysis.
  • Activation of ERK-1/2 and STAT3 was assessed by measuring their respective phosphorylation states.

Main Results:

  • Hcy induced a dose-dependent increase in AT1 receptor expression in MAECs, with significant elevation at 100 μM after 48 hours.
  • Hcy-mediated activation of AT1 receptor led to subsequent phosphorylation of ERK-1/2 and STAT3.
  • STAT3 activation was found to regulate Hcy-induced MMP-9 and collagen type-1 expression, effects attenuated by an AT1 receptor blocker (valsartan) and a STAT3 inhibitor.

Conclusions:

  • This study provides the first evidence for the involvement of the AT1 receptor in HHcy-induced atherosclerotic diseases.
  • HHcy activates the AT1 receptor, which subsequently modulates MMP-9 and collagen type-1 expression through ERK-1/2 and STAT3 signaling cascades, contributing to vascular remodeling.
Abstract

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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...
Hypertension II: Pathophysiology01:29

Hypertension II: Pathophysiology

Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

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...
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers01:19

Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers

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...
Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

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...