72 - NOVEL INSIGHTS INTO KAWASAKI DISEASE PATHOLOGY: DYNAMIC CHANGES IN VENTRICULAR WALLS INVOLVING FIBROBLASTS/FIBROSIS AND ADIPOCYTES

Background/Aim: Myocardial fibrosis is noted on KD autopsies but has not been systematically studied.

Methods: We analyzed six hearts from KD autopsies and KD transplanted hearts using conventional histology and immunohistochemistry. Interval between disease onset and autopsy/transplant varied from 10 months to 30 years.

Results: Myocardial samples varied in the distribution and extent of fibrosis, which was mainly found around pericoronary regions and/or the ventricular interstitium, and displayed traits of both diffuse and focal/substitutive fibrosis throughout the ventricular transmural axis (epicardium to endocardium). Moreover, we identified a different spatio-temporal expression pattern for two extracellular matrix proteins (asporin -ASPN- and periostin -POSTN-). ASPN was located surrounding interstitial fibrotic regions, internally delimiting the fibrotic area, but did not associate with adipocytes. In contrast, POSTN was mainly deposited in well-defined interstitial fibrotic domains, distributing either diffusely between cardiomyocytes or forming small interstitial fibrotic foci. In some patients, POSTN was also massively expressed in the perivascular regions of larger subepicardial vessels and the ventricular interstitium, where it was closely associated with adipocytes. Finally, we also identified an unexpected distribution of adipocytes within the myocardial wall layers; adipocytes were found either distributed around coronary vessels or integrated as part of the core of fibrotic foci. The expression of perlipin (PLPN) revealed variable degrees of adipocyte maturation. All these results, taken together, suggest that cardiac fibrosis. in KD patients is a progressive and dynamic phenomenon. Accordingly, in order to classify these KD samples, we propose a simple score (0-3) based on the heterogeneous nature of the cardiac fibrotic tissue (ASPN or POSTN expression patterns) and the distribution and maturation of adipocytes (Table 1).

Conclusions: Our findings open new avenues for the identification of key mechanisms in cardiac pathology associated with KD, and suggest chronic, on-going remodeling of the myocardium. Although we cannot eliminate ischemia due to aneurysms as the main cause of the fibrosis in these KD patients, the observed pathology differs from the typical ventricular remodeling process that is associated with other chronic or acute ischemic events, such as hypertrophy and myocardial infarction, opening the possibilities to other potential, unknown origins for this cardiac fibrotic process.