Active calcium deposition is not associated with microcalcification in the cardiac tissue of transthyretin cardiac amyloidosis patients.
Cardiac amyloidosis is a pathological condition characterized by the deposition of amyloid, an insoluble protein with abundant β-sheet structures, within the heart, leading to the manifestation of heart failure symptoms. The primary forms of cardiac amyloidosis consist of transthyretin cardiac amyloidosis (ATTR-CA), which is attributed to the presence of transthyretin (TTR) as the amyloidogenic precursor, and amyloid light-chain cardiac amyloidosis (AL-CA), in which the light immunoglobulin chains are the amyloidogenic precursor. ATTR-CA is associated with high uptake of Tc-labeled bone tracers in the heart.
A study published in the International Journal of Molecular Sciences assessed the mechanisms of uptake of bone tracer along microcalcification in the cardiac tissue of ATTR-CA patients at molecular and histological levels and found that microcalcification in the cardiac tissue of ATTR-CA patients is not associated with active calcification-promoting mechanisms.
New Findings Reveal Unusual Calcification Pattern in ATTR-CA Patients
The current study found higher uptake of Tc-PYP in the cardiac tissue of ATTR-CA patients, compared with non-cardiac amyloidosis (non-CA) and AL-CA patients. The ATTR-CA patients exhibited a higher frequency of endomyocardial von Kossa-positive microparticles in the biopsy samples. These patients also exhibited calcified particles on the endomyocardial biopsy on electron microscopy in the sites of collagen fibers instead of amyloid fibers. There was no mitochondrial calcification in the hearts of ATTR-CA patients.
Higher Bone Tracer Uptake in the Hearts of ATTR-CA Patients
No increase was observed in the expression of bone metabolism-associated genes in the cardiac tissue of ATTR-CA patients. Only AL-CA patients had a noticeable increase in the expression of SPP1, which is linked to chronic inflammation in cardiac tissues. The study proposes a connection between microcalcification and passive calcium deposition in the cardiac tissue of ATTR-CA patients. Nevertheless, no substantial evidence was found to support a greater uptake of bone tracers in the heart compared to the bones of ATTR-CA patients.
Cardiac Calcification Not Linked to Active Calcification-Promoting Mechanisms
As supported by the lack of elevated gene expression related to bone metabolism, active calcification-promoting mechanisms are not responsible for calcified microparticles in the cardiac tissue of ATTR-CA patients. The reason behind the stronger uptake of bone tracer in the heart, as opposed to the ribs, requires further examination.
Mori, A., Saito, Y., Nakamura, K., Iida, T., Akagi, S., Yoshida, M., Taniyama, M., et al. (2023). Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis. International Journal of Molecular Sciences, 24(3), 1921. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms24031921