Monosodium Urate Crystals within Cardiomyocytes

BackgroundWhile monosodium urate (MSU) crystal deposition within coronary plaques links hyperuricemia/gout to cardiovascular risk, the existence and functional consequences of MSU deposits within the myocardial interstitium or cardiomyocytes remain unknown. MethodsForensic autopsy myocardial and renal specimens from gout patients (n=4) and controls (n=4) were analyzed for MSU crystals using compensated polarized microscopy, laser capture microdissection coupled with HPLC-MS, and cryo-electron microscopy (cryo-EM) with electron diffraction. Pharmacological (adenine-diet) and genetic (Uox-/-) hyperuricemia murine models were assessed by crystal detection, echocardiography, and correlative histopathology. ResultsMyocardial MSU crystals were identified in all human gout cases (absent in controls), localized perivascularly, interstitially, and intracellularly within cardiomyocytes. Definitive verification was provided by compositional analysis (HPLC-MS m/z 167) and crystal structure confirmation (cryo-EM diffraction matching MSU). Hyperuricemic mice exhibited myocardial MSU deposition, progressive diastolic dysfunction (r =0.7014 vs. crystal burden), and reduced survival associated with higher crystal load. Importantly, myocardial crystal burden correlated more strongly with cardiac impairment than serum uric acid levels. ConclusionThis study provides conclusive morphological, chemical, and crystallographic evidence of intracardiac MSU deposition in gout. It directly links myocardial crystal accumulation to diastolic dysfunction, proposing "uric acid cardiomyopathy" as a novel disease entity. Collectively, these findings achieve a paradigm shift in the perception of gout, redefining it from a peripheral arthropathy to a systemic disorder capable of causing direct myocardial injury.