Doença mixomatosa da valva mitral: Mensuração ecocardiográfica / Mitral valve disease due to myxomatous degeneration (MMVD): Echocardiographic  measurement

Abstract Introduction Mitral valve disease (MVD) is a frequent cause of heart failure and death. Data regarding its molecular basis are scarce, although current evidences show that primary MVD is an active process with the involvement of several molecular pathways. However, there are no studies that compare such mechanisms among the different subtypes of primary MVD. ST-2/interleukin (IL)-33 pathway is a potential pathophysiological mediator of cardiovascular diseases, although its role in heart valve diseases has not been explored. Purpose We aimed to analyse the molecular and cellular mechanisms involved in the main subtypes of primary chronic MVD: myxomatous degeneration, calcific or senile degeneration and rheumatic MVD. Methods 200 patients undergoing mitral valve replacement due to chronic primary MVD were enrolled. We classified them in the three main aetiologic subtypes according to echocardiographic features and surgeon's description: myxomatous degeneration (89 patients), senile or calcific degeneration (54 patients) and rheumatic disease (57 patients). In all patients the resected valve tissue and blood samples were collected. RT-PCR, Western Blot and ELISA were performed to analyse markers of inflammation (C-reactive protein, Rantes, IL-6, IL-1β/IL-1F2, tumor necrosis factor (TNF)-α), calcification (osteopontin, bone morphogenic protein (BMP)-2 and -4 and periostin), valvular endothelial cells (CD-31, E-cadherin), extracellular matrix remodeling (matrix metalloproteinase (MMP)-1, -2 and -9, tissue inhibitor of MMP-1 and -2), proteoglycans (aggrecan, hyaluronan, lumican, biglycan, syndecan-1, decorin) fibrosis (collagen-1, fibronectin, galectin-3, Transforming growth factor (TGF)-β) and ST-2/IL-33 system. Results Each aetiologic subtype showed a distinct marker profile. As compared with the other subtypes, myxomatous valves presented significantly higher levels of inflammatory markers (Rantes, IL-6), fibronectin, proteoglycans (hyaluronan, lumican and biglycan), ST-2 and IL-33. Senile degenerative valves presented significantly higher levels of calcification markers (osteopontin, BMP-2 and -4). Rheumatic valves were characterized by high levels of TNF-α and TGF-β compared to other subtypes and a significant increase in the expression and activity of matrix degradation enzymes (MMP-1 and -2). Conclusions Our study provides for the first time the molecular characterisation of the main aetiologic subtypes of chronic MVD. Proteoglycans accumulation, fibrosis and inflammation are the main features of myxomatous changes, whereas calcification define senile degeneration. Rheumatic valves exhibit elevated TNF-α and TGF-β and a dramatic increase in matrix turnover. Moreover, myxomatous valves overexpress the ST-2/IL-33 system, suggesting that this pathway could play a role in the development of myxomatous changes. Unravelling the underlying molecular mechanisms of each aetiology is essential to identify new therapeutic targets. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fondo de Investigaciones Sanitarias

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Perspectives on surgical treatment of mitral valve disease

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492320930846 ◽

2020 ◽

Vol 28 (7) ◽

pp. 360-365

Author(s):

Tirone E David

Keyword(s):

Developing Countries ◽

Mitral Valve ◽

Mitral Valve Disease ◽

Functional Anatomy ◽

Developed Countries ◽

Valve Disease ◽

Pathological Changes ◽

Valve Dysfunction ◽

Myxomatous Degeneration ◽

Better Than

A sound knowledge of the functional anatomy of the mitral valve and the alterations caused by different diseases is indispensable for surgeons treating patients with mitral valve disease. Rheumatic mitral valve disease remains the most common heart valvular disorder in developing countries, whereas mitral regurgitation due myxomatous degeneration of the valve is the most common in developed countries. The mitral valve should be repaired whenever possible, as long as the outcome is predictably better than that of replacement. The intraoperative decision to repair or replace is not always simple and depends on the experience of the surgeon and the pathological changes that caused mitral valve dysfunction.

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Clinical-imagistic correlations in dogs with myxomatous mitral valve disease

Practica Veterinara ro ◽

10.26416/pv.30.1.2018.1588 ◽

2018 ◽

Vol 1 (1) ◽

pp. 23-31

Author(s):

Călin Șerdean ◽

Alexandra Mihaela Popa ◽

Mario Codreanu

Keyword(s):

Mitral Valve ◽

Mitral Valve Disease ◽

Severe Heart Failure ◽

Mitral Valve Insufficiency ◽

Valvular Disease ◽

Valve Disease ◽

Echocardiographic Examination ◽

Valve Insufficiency ◽

Myxomatous Degeneration ◽

Yorkshire Terrier

Myxomatous mitral valve disease (MMVD; degenerative valvular disease, endocardiosis, chronic valvular disease) is one of the most common acquired cardiac disease of dogs (75-80% from the cardiac diseases), characterized by mitral valve insufficiency. Pathologically, it is characterized by myxomatous degeneration of leaflets which does not have a congenital aspect, and that can progress to prolapse of one or both leaflets toward the left atrium during systole, and severe heart failure. It seems that the diseases is age and breed dependent. In most of the cases, MMVD occurs in dogs older than 5-8 years old and progresses as the dogs get older. The most predispose breed is Cavalier King Charles Spaniel, followed by Poodle (miniature and toy), Bichon, Lhassa Apso, Shih Tzu, Miniature Schnauzer, Cocker Spaniel, Chihuahua, Fox Terrier, Beagle, Pekinese, Dachshund, Yorkshire Terrier and Boston Terrier. This study aims to correlate the clinical and paraclinical examinations with the changes found in the echocardiographic examination.

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Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22052310 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2310

Author(s):

Amaia Garcia-Pena ◽

Jaime Ibarrola ◽

Adela Navarro ◽

Alba Sadaba ◽

Carolina Tiraplegui ◽

...

Keyword(s):

Extracellular Matrix ◽

Mitral Valve ◽

Mitral Valve Disease ◽

Valve Disease ◽

Proteoglycan Synthesis ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Mesenchymal Transition ◽

Interleukin 33 ◽

Myxomatous Degeneration

Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valve has not been investigated. We aim to explore IL-33 as a possible inductor of myxomatous degeneration in human mitral valves. We enrolled 103 patients suffering from severe mitral regurgitation due to myxomatous degeneration undergoing mitral valve replacement. Immunohistochemistry of the resected leaflets showed IL-33 and ST2 expression in both valve interstitial cells (VICs) and valve endothelial cells (VECs). Positive correlations were found between the levels of IL-33 and molecules implicated in the development of myxomatous MVD, such as proteoglycans, extracellular matrix remodeling enzymes (matrix metalloproteinases and their tissue inhibitors), inflammatory and fibrotic markers. Stimulation of single cell cultures of VICs and VECs with recombinant human IL-33 induced the expression of activated VIC markers, endothelial–mesenchymal transition of VECs, proteoglycan synthesis, inflammatory molecules and extracellular matrix turnover. Our findings suggest that the IL-33/ST2 system may be involved in the development of myxomatous MVD by enhancing extracellular matrix remodeling.

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