Doxycycline decreases amyloidogenic light chain-induced autophagy in isolated primary cardiac myocytes.
Int J Cardiol
; 321: 133-136, 2020 12 15.
Article
en En
| MEDLINE
| ID: mdl-32682005
ABSTRACT
BACKGROUND:
Immunoglobulin light chain (AL) cardiac amyloidosis is characterized by extracellular deposition of amyloid fibrils in the heart and is potentially fatal. Untreated, it manifests clinically as heart failure with a precipitous decline and a median survival of <6â¯months. AL cardiac amyloidosis is associated with impaired extracellular matrix homeostasis in the heart with increased matrix metalloproteinase (MMP) levels. This commmunication provides novel insights into a potential role for doxycycline, a non-selective MMP inhibitor in AL cardiac amyloidosis. METHODS/RESULTS:
Adult rat ventricular myocytes stimulated with AL (obtained from cardiac amyloidosis patients) increased MMP-2 and MMP-9 activities (Pâ¯<â¯.05); the expression of autophagy marker microtubule associated protein 1 LC-3 isoform II (LC3-II) (Pâ¯<â¯.01), and the autophagy-related proteins ATG-4B (Pâ¯<â¯.05) and ATG-5 (P <â¯.05) as compared to untreated cardiomyocytes. Doxycycline abrogated MMP activities (Pâ¯<â¯.0001) and decreased AL-induced autophagy via ATG-5 (Pâ¯<â¯.05).CONCLUSIONS:
These in vitro studies demonstrated that doxycycline, in addition to inhibiting MMP, also modulated AL-induced autophagy in cardiomyocytes and provide potential insights for future therapeutic targets for AL-induced proteotoxicity. Novel therapies for cardiotoxicity and heart failure in AL cardiac amyloidosis remain an important unmet need.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Miocitos Cardíacos
/
Amiloidosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cardiol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos