Work

Impaired coronary flow reserve by hyperviscosity in a mouse model of non-light chain multiple myeloma: a mechanism of coronary flow impairment at the capillary level

Year: 2025

Type: article

Abstract: AIMS: Multiple myeloma (MM) is associated with cardiovascular risk, although the exact underlying mechanisms are unknown. Here, we tested the hypothesis that MM impairs coronary flow reserve (CFR) due to increased blood viscosity caused by elevated monoclonal protein concentration. METHODS AND RESULTS: In a mouse Vĸ*MYC model of non-light chain MM recapitulating all aspects of human disease, we showed that the disease progression was associated with progressive increase of blood and plasma viscosity. Using intravital microscopy imaging of ex vivo stained red blood cells, we observed reduction of CFR in vivo with the CFR limiting site being coronary capillaries. This was further confirmed by similar coronary flow profile in mice with hyperviscosity induced by acute hyperlipidaemia and disappearance of this MM-related CFR impairment in saline perfused ex vivo hearts. Of note, nitric oxide production in vivo was increased in the coronary circulation, especially at the capillary level, but the systemic concentration of nitric oxide metabolites was unchanged, again supporting the hypothesis that increased blood viscosity is the main culprit here. Moreover, MM progression was associated with progressive impairment of left and right ventricular function, but without histological signs of myocardial deterioration, hypertrophy, or fibrosis. CONCLUSION: Our study shows a potentially completely new mechanism of cardiovascular adverse effects caused by MM or more broadly by hyperviscosity syndromes, i.e. CFR impairment at the capillary level. Since capillaries, unlike larger vessels, cannot be recanalized or dilated, completely new preventive approaches are needed, such as agents affecting blood rheology.

Source: Cardiovascular Research

DOI: 10.1093/cvr/cvaf164