Peripheral blood contains numerous mRNAs that have the potential to influence cardiac physiology. Although stage B2 Myxomatous Mitral Valve Disease (MMVD) is known to involve prolonged hemodynamic stress and remodeling of cardiac chambers due to mitral regurgitation, the gene-expression alterations present in the blood of affected dogs have not yet been clearly defined. To explore these changes, we compared the blood transcriptomes of healthy dogs (NC) with those of dogs naturally diagnosed with stage B2 MMVD. High-throughput sequencing followed by Weighted Gene Co-expression Network Analysis (WGCNA) and functional enrichment analyses (GO and KEGG) revealed a “turquoise” gene module that showed the strongest association with echocardiographic measurements. Within this module, 64 genes were differentially expressed and predominantly mapped to pathways involved in platelet activation. From these, five genes—MDM2, ROCK1, RIPK1, SNAP23, and ARHGAP35—were chosen for further examination. qPCR validation showed that four of them (MDM2, ROCK1, RIPK1, and SNAP23) displayed significant expression differences (P < 0.01) between MMVD and control dogs. Additionally, correlation analyses indicated that these four genes were inversely related to several cardiac structural indices, mirroring the trends observed in the WGCNA output. Our investigation highlights four platelet activation–associated genes—MDM2, ROCK1, RIPK1, and SNAP23—as potential blood-based biomarkers for identifying stage B2 MMVD. These results enhance understanding of the molecular changes accompanying early disease progression.
