Related Experiment Video

Updated: Mar 28, 2026

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction
08:35

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction

Published on: August 17, 2022

3.4K

Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction

Constantijn Franssen1, Sophia Chen1, Andreas Unger2

  • 1Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.

JACC. Heart Failure
|December 20, 2015
PubMed

Insights

Metabolic risk causes heart failure with preserved ejection fraction (HFpEF) through inflamed coronary microvascular endothelial activation. This impairs nitric oxide (NO) signaling to heart cells, increasing stiffness and hypertrophy.

Area of Science:

  • Cardiovascular Medicine
  • Molecular Biology
  • Pathophysiology

Background:

  • Metabolic risk factors are linked to diastolic left ventricular (LV) dysfunction.
  • Diastolic LV dysfunction is a hallmark of heart failure with preserved ejection fraction (HFpEF).

Purpose of the Study:

  • To investigate if metabolic risk-induced, low-grade inflammation contributes to HFpEF.
  • To explore the role of coronary microvascular endothelial activation in this process.
  • To determine the impact on cardiomyocyte signaling, hypertrophy, and diastolic stiffness.

Main Methods:

  • Examined inflammatory endothelial activation in myocardial biopsies from HFpEF patients.
  • Assessed oxidative stress, nitric oxide (NO) bioavailability, and cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling.
  • Validated findings in obese Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1)-HFpEF rats compared to controls.

Main Results:

  • Upregulated E-selectin and intercellular adhesion molecule-1 expression in HFpEF myocardium.
  • Increased NADPH oxidase 2 expression in macrophages and endothelial cells, not cardiomyocytes.
  • Uncoupled endothelial nitric oxide synthase with reduced myocardial nitrite/nitrate, cGMP, and PKG activity.

Conclusions:

  • HFpEF is associated with coronary microvascular endothelial activation and oxidative stress.
  • These factors reduce NO-dependent signaling from endothelial cells to cardiomyocytes.
  • This impaired signaling contributes to cardiomyocyte stiffness and hypertrophy in HFpEF.
Abstract

Keywords:
endotheliumheart failureinflammationnitric oxideoxidative stress

Related Concept Videos

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...
1.4K
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...
4.5K
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
568
Heart Failure I: Introduction01:27

Heart Failure I: Introduction

Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
1.2K
Imbalances in Cardiac Output01:26

Imbalances in Cardiac Output

The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
3.4K
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
955