Fibrillin and other matrix proteins in mitral valve prolapse syndrome

Joseph F Nasuti1, Paul J Zhang, Michael D Feldman

  • 1Hospital of University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Insights

Abnormalities in fibrillin and other matrix proteins likely cause myxomatous degeneration in mitral valve prolapse syndrome (MVPS). This study found distinct extracellular matrix protein distribution differences in MVPS leaflets compared to normal and rheumatic heart disease valves.

Area of Science:

  • Cardiovascular Biology
  • Extracellular Matrix Research
  • Molecular Pathology

Background:

  • Myxomatous degeneration in Marfan syndrome is linked to fibrillin gene mutations.
  • The molecular cause of myxomatous degeneration in mitral valve prolapse syndrome (MVPS) remains unclear.
  • This study investigates extracellular matrix protein distribution in isolated MVPS.

Purpose of the Study:

  • To examine the distribution of fibrillin and other extracellular matrix proteins in mitral valve leaflets from patients with isolated MVPS.
  • To compare these distributions with those in normal mitral valves and valves affected by rheumatic heart disease (RHD).

Main Methods:

  • Immunohistochemical analysis of mitral valve leaflets from 7 MVPS patients, 5 RHD patients, and 5 normal controls.
  • Characterization of fibrillin, elastin, collagen I, and collagen III distribution.

Main Results:

  • Normal valves show a laminar pattern of fibrillin, elastin, and collagens.
  • MVPS leaflets with myxoid degeneration exhibit diffuse, weaker, and nonlaminar staining for fibrillin and other matrix proteins.
  • RHD valves show localized disruption of extracellular proteins, preserving overall architecture, unlike the diffuse changes in MVPS.

Conclusions:

  • Abnormalities in fibrillin and other extracellular matrix proteins play a primary role in myxoid degeneration of mitral valve leaflets in MVPS.
  • These findings highlight a distinct molecular basis for MVPS compared to other valvular diseases.

Related Concept Videos

Mitral Valve Prolapse I: Introduction01:27

Mitral Valve Prolapse I: Introduction

IntroductionThe mitral valve, one of the heart's four valves, regulates blood flow. These valves have flaps that open and close to direct blood properly through the heart and body. During each heartbeat, the flaps open for blood to pass through and seal shut to prevent backflow. Specifically, the mitral valve opens to allow blood flow from the heart's upper left chamber to the lower left chamber. It then closes securely as the lower left chamber contracts to pump blood to the body, preventing...
Mitral Valve Prolapse II: Assessment and Management01:22

Mitral Valve Prolapse II: Assessment and Management

IntroductionA range of clinical features characterizes Mitral Valve Prolapse (MVP), but it is important to note that many individuals with MVP are asymptomatic and may remain so throughout their lives. For those who do exhibit symptoms, the following are the key clinical features:Palpitations: This is a common symptom where individuals feel an irregular or rapid heartbeat. Palpitations in MVP are often due to arrhythmias such as premature ventricular contractions or supraventricular tachycardia.
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...
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
Mitral Regurgitation I: Introduction01:20

Mitral Regurgitation I: Introduction

Mitral regurgitation is characterized by the backward circulation of blood from the left ventricle to the left atrium during systole, a phase of the cardiac cycle when the heart contracts and pumps blood out of the chambers. This abnormal flow occurs primarily due to the dysfunction of the mitral valve or its supporting structures, which include the mitral leaflets, chordae tendineae, annulus, and papillary muscles.Etiology and Mechanisms:Primary Mitral Regurgitation: This type arises from...