Author(s): DUSSAUGE, M., NOGUER, M., MERLET, A., BERTHON, P., HELLSTEN, Y., MESSONNIER, L., Institution: UNIVERSITE SAVOIE MONT BLANC , Country: FRANCE, Abstract-ID: 2575

INTRODUCTION:
Lactate is now recognized as a key signaling molecule with angiogenic properties in various tissues, including the brain and tumors, acting through the transporter MCT1 and the receptor HCAR1. Given that skeletal muscle produces large amounts of lactate during contraction, we hypothesized that lactate may act as a local regulator of microvascular remodeling in this tissue. To test this hypothesis, we investigated skeletal muscle microvascular adaptations in MCT1+/- mice, a model of partial MCT1 deficiency associated with chronically elevated resting lactate levels.
METHODS:
Eleven MCT1+/- mice were compared with eight wild-type (WT) mice. Gastrocnemius (GAS) and soleus (SOL) muscles were harvested. Morphometric analyses of the microvasculature and HCAR1 localization were performed in GAS using immunofluorescence. HCAR1 protein content was quantified by western blot in GAS and SOL.
RESULTS:
Histological analyses revealed higher capillary density (p = 0.04), a higher number of capillaries in contact with a muscle fiber (CAF) (p = 0.022), higher CAF relative to fiber surface area (p = 0.027), and a greater length of contact-to-fiber perimeter ratio (p = 0.022) in MCT1+/- mice compared with WT. No significant differences were observed in capillary morphology (tortuosity or diameter). Immunofluorescence showed HCAR1 expression in skeletal muscle of both groups, localized predominantly in endothelial cells and, to a lesser extent, at the sarcolemma. HCAR1 protein content was significantly higher in SOL of MCT1+/- mice (p = 0.042), with a trend toward higher levels in GAS (p = 0.07).
CONCLUSION:
Reduced MCT1 expression was associated with enhanced microvascular remodeling, reflected by increased quantitative indices of microcirculation. This remodeling was accompanied by elevated HCAR1 protein content, predominantly expressed in capillaries and to a lesser extent at the sarcolemma. Chronically elevated resting lactate levels may contribute to these adaptations through HCAR1-mediated signaling. Further studies are needed to better understand the mechanisms underlying this microvascular remodeling.