Doxycycline decreases amyloidogenic light chain-induced autophagy in isolated primary cardiac myocytes.

International Journal of Cardiology
María Valero-MuñozFlora Sam

Abstract

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 <6 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. Adult rat ventricular myocytes stimulated with AL (obtained from cardiac amyloidosis patients) increased MMP-2 and MMP-9 activities (P < .05); the expression of autophagy marker microtubule associated protein 1 LC-3 isoform II (LC3-II) (P < .01), and the autophagy-related proteins ATG-4B (P < .05) and ATG-5 (P < .05) as compared to untreated cardiomyocytes. Doxycycline abrogated MMP activities (P < .0001) and decreased AL-induced autophagy via ATG-5 (P < .05). 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 prote...Continue Reading

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Citations

Dec 29, 2020·International Journal of Cardiology·Lian-Jie HouGuo-Jun Zhao
Jan 31, 2021·International Journal of Cardiology·María Valero-Muñoz, Flora Sam
May 17, 2021·Blood Cancer Journal·M Hasib Sidiqi, Morie A Gertz

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