Apelin and its receptor APJ in human aortic valve stenosis

Tuomas Peltonen1, Juha Näpänkangas, Olli Vuolteenaho

  • 1Department of Pharmacology and Toxicology, University of Oulu, Biocenter Oulu, Finland.

Insights

Aortic valve stenosis shows increased apelin-APJ signaling, suggesting a new therapeutic target for calcified aortic valve disease by inhibiting key disease processes.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pathology

Background:

  • Aortic valve stenosis (AS) shares characteristics with atherosclerosis.
  • The apelin-APJ system's role in AS is currently unknown.
  • Apelin-APJ signaling may oppose the angiotensin II-AT1-receptor pathway.

Purpose of the Study:

  • To investigate the role of the apelin-APJ signaling pathway in aortic valve stenosis.
  • To compare expression of apelin, APJ, and angiotensin II receptors in normal and diseased aortic valves.

Main Methods:

  • Analyzed aortic valve tissue from patients with normal valves, aortic regurgitation (AR), AR with sclerosis, and AS.
  • Utilized reverse-transcriptase polymerase chain reaction (RT-PCR) for gene expression analysis.
  • Employed immunohistochemistry to determine protein localization.

Main Results:

  • Apelin and APJ receptor gene expression were significantly upregulated in stenotic valves.
  • APJ receptor mRNA levels were also higher in valves with AR and sclerosis.
  • AT2 receptor mRNA levels were significantly lower in stenotic valves, while AT1 receptor expression did not differ.

Conclusions:

  • Aortic valve stenosis is associated with increased apelin-APJ signaling.
  • This pathway represents a potential novel drug target for calcified aortic valve disease.
  • Targeting this pathway could suppress disease processes like chemotaxis, angiogenesis, and osteoblast activity.
Abstract

Related Concept Videos

Aortic Regurgitation I: Introduction01:15

Aortic Regurgitation I: Introduction

IntroductionAortic regurgitation is characterized by the backward flow of blood from the aorta into the left ventricle during diastole and arises from the improper closure of the aortic valve. This condition results in left ventricular volume overload and can stem from both acute and chronic etiologies, each contributing uniquely to the disease's progression and symptomatology.Acute and Chronic CausesAcute aortic regurgitation often results from events that suddenly impair the integrity of the...
Aortic Regurgitation III: Medical Management01:25

Aortic Regurgitation III: Medical Management

Aortic regurgitation (AR) is when the aortic valve does not close or seal properly, leading to backward blood circulation from the aorta into the left ventricle during diastole. Common causes of AR include rheumatic heart disease, congenital valve defects, and aortic root dilation. Managing AR requires a multifaceted approach to alleviate symptoms, preserve left ventricular function, and address the underlying cause of the regurgitation. Patients with symptomatic AR or significant left...
Heart Valves01:16

Heart Valves

The human heart is a complex organ with an intricate system of valves that regulate blood flow. There are two main types of valves: atrioventricular (AV) valves and semilunar valves.
The AV valves prevent the backflow of blood from the ventricles to the atria during ventricular contraction. These valves function with the assistance of the chordae tendineae and papillary muscles. When the ventricles are relaxed, the chordae tendineae are slack, allowing blood to flow from the atria into the...
Aortic Regurgitation II: Clinical Features and Diagnostic Tests01:22

Aortic Regurgitation II: Clinical Features and Diagnostic Tests

Aortic valve regurgitation (AR) occurs when the aortic valve fails to close properly, allowing blood to flow backward from the aorta into the left ventricle. This backflow can result in two distinct clinical presentations: acute and chronic AR, each characterized by its own set of symptoms and physical findings.Acute Aortic RegurgitationAcute AR presents with a sudden onset of severe symptoms. Patients typically experience profound dyspnea (shortness of breath), chest pain, and signs of left...
Mitral Stenosis I: Introduction01:22

Mitral Stenosis I: Introduction

Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...