Therapeutic Impact of Vericiguat on Ventricular Remodeling in a Pressure-Overload Heart Failure Model

Figure 1. Vericiguat restores ventricular wall stress in pressure-overload heart failure. Representative M-mode echocardiographic images (A) and quantitative analysis of dynamic wall stress (DWS; (B)) are shown for Sham, transverse aortic constriction (TAC), and TAC + Vericiguat (Veri) groups. TAC significantly reduced DWS compared with Sham (*** p < 0.001), indicating impaired ventricular biomechanics. Vericiguat treatment restored DWS toward baseline (### p < 0.001 vs. TAC), reflecting improved contractility and normalization of wall stress regulation. Data are presented as mean ± SD; n = 6 per group.

Figure 2. Vericiguat attenuates cardiac hypertrophy induced by pressure overload. Representative images of excised hearts (A) and quantification of heart weight normalized to body weight (B) and tibia length (C) are shown for Sham, transverse aortic constriction (TAC), and TAC + Vericiguat (Veri) groups. TAC induced significant cardiac enlargement compared with Sham (*** p < 0.001), whereas Vericiguat markedly reduced heart size and weight (## p < 0.01, ### p < 0.001 vs. TAC). Normalization to tibia length (C) was included to avoid potential bias introduced by post-surgical changes in body weight and to strengthen the robustness of hypertrophy assessment. Data are presented as mean ± SD; n = 6 per group.

Figure 3. Vericiguat reduces myocardial fibrosis in pressure-overload heart failure. (A) Representative histological sections of left ventricular tissue stained with Masson’s trichrome (top row) and Picrosirius red (bottom row) from Sham, transverse aortic constriction (TAC), and TAC + Vericiguat (Veri) groups. Collagen deposition appears as blue in Masson’s trichrome and as red birefringence under polarized light in Picrosirius red. (B) Quantitative analysis of fibrotic area (%) from Masson’s trichrome and (C) Picrosirius red staining. TAC significantly increased myocardial fibrosis compared with Sham (*** p < 0.001), whereas Vericiguat markedly reduced fibrotic burden (## p < 0.01 vs. TAC). Data are presented as mean ± SD; n = 6 per group.

Figure 4. Vericiguat reprograms the fibroblast proteome in pressure-overload heart failure. Hierarchical heatmap of differentially expressed proteins (DEPs) in fibroblast-enriched cardiac tissue across four experimental groups: wild-type (WT), sham-operated (Sham), transverse aortic constriction (TAC), and TAC + Vericiguat (TAC-Ver). Protein abundance is color-coded (green: low; black: intermediate; red: high) and clustered by expression similarity. TAC markedly altered fibroblast proteomic profiles, with upregulation of pro-fibrotic and inflammatory markers and suppression of mitochondrial and reparative proteins. Vericiguat reversed these changes, restoring expression of bioenergetic, structural, and reparative components. These findings indicate that Vericiguat modulates fibroblast activity and extracellular matrix remodeling through targeted proteomic reprogramming.

Figure 5. Vericiguat modulates myocyte proteomic signatures in pressure-overload heart failure. Hierarchical heatmap of differentially expressed proteins (DEPs) in myocyte-enriched cardiac tissue across four groups: wild-type (WT), sham-operated (Sham), transverse aortic constriction (TAC), and TAC + Vericiguat (TAC-Ver). Protein abundance is color-coded (green: low; black: intermediate; red: high) and clustered by expression similarity. TAC-induced pressure overload disrupted myocyte proteomic profiles, with downregulation of mitochondrial enzymes, contractile proteins, and calcium-handling components. Vericiguat reversed these alterations, restoring expression of bioenergetic and structural proteins. These findings suggest that Vericiguat preserves myocyte integrity and function through targeted proteomic reprogramming under pathological stress.