Cardiac Amyloid in Experimental AA Amyloidosis is Associated with IncreasedAutophagic Activity
(English)Manuscript (preprint) (Other academic)
Cardiac involvement in reactive amyloidosis is a severe complication that leads to reducedsurvival. We induced reactive amyloidosis in mice by induction of chronic inflammation andfound that cardiac involvement develops later than spleen and liver deposits. TEM studiesrevealed intracellular amyloid deposits, but endogenous production of SAA1, SAA2 or SAA3by the cardiomyocytes was not supported by mRNA analysis. Therefore, the intracellulardeposits of protein AA must derive from SAA produced at another location. Autophagosomeswere present in close association with intracellular amyloid and the autophagy marker LC3was increased 20 times in cardiac tissue with moderate amounts of amyloid. Increase in LC3was not paralleled by an increase in LAMP-2. The ER-stress marker Bip was unchanged ininflamed heart tissue and in amyloid-containing heart. Even though procaspase-12 increasedin heart after silver nitrate injections and in heart with AA-amyloid, no active caspase-12could be detected. We suggest that autophagosomes are involved in amyloid clearance, buttheir accumulation indicate that the formation of autophagolysosomes is hampered.
AA-amyloid, cardiomyocytes, autophagy, Amyloid enhancing factor (AEF)
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-20808OAI: oai:DiVA.org:liu-20808DiVA: diva2:236166