Deep Crotonylproteomics Analysis of High-Altitude Exposure Hearts in Mice

The potential molecular mechanisms of short-term adaptation and long-term structural deteriorations in the cardiac structure in response to high altitude remain not fully understood. This study aims to investigate changes in the crotonylproteome in the hearts of mice exposed to high altitude at different time points. The hearts were obtained from mice living at the lowland and 3, 10, and 30 days after arriving at a plateau. Crotonyllysolylated proteins were subsequently comprehensively evaluated. Among the identified 13,731 crotonyllysine sites, 11,140 were quantified. Furthermore, 1247 differentially expressed crotonyllysine sites on 764 proteins in 46 pathways were analyzed, and the results showed that the abundance of crotonylation increased with the increase of exposure time to altitude. Functional enrichment analysis showed that most of these significantly altered crotonylated proteins were enriched in the regulation of metabolism and myocardial function, indicating that these enriched biological processes may be involved in the acute adaptation and chronic remodeling of cardiac function and structural changes at a high altitude. Our study uncovers some crotonylation-affected processes and pathways in the heart's response to high-altitude exposure, giving novel insights into molecular processes of cardiac function and structure changes at high altitude (ProteomeXchange identifier: PXD044178).