Pip4k2c modRNA elevates Pip4k2c levels, attenuating cardiac hypertrophy and fibrosis post TAC injury. a) Experimental timeline to evaluate Pip4k2c modRNA expression and cardiac function in TAC mouse model. b) Western blot of Luc (control) or Pip4k2c modRNA expression in mouse hearts 24 hours post TAC (n = 2) and quantitative analysis thereof (n = 2). c. Representative echocardiography image of left ventricle 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA. d–g) Echo evaluation of delta % left ventricular ejection fraction (d), fractioning shorting (e), LVIDd (f), and LVIDs (g) before (day 0), 14, or 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA (n = 8). h) Representative images of whole heart 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA. i) Heart weight to tibia length 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA (n = 8). j) Representative images of WGA staining to evaluate CM size (cross‐sectional area) 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA. k) Quantitative analysis of j (n = 8). l) qPCR analysis of hypertrophic markers 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA (n = 5). m) Representative images of Sirius red / fast green to evaluate fibrotic area 21 days post TAC injury and delivery of Luc or Pip4k2c modRNA. n) Quantitative analysis of m (n = 8). o,p) qPCR analysis of TGFβ1 and its downstream target genes (o, n = 5) or different matrix metalloprotease (MMP) genes (p, n = 5). q) Survival curve of mice post TAC injury and delivery of Luc or Pip4k2c modRNA (n = 10). Unpaired two‐tailed t‐test for c, e–g, i, k,l, n–p. Mantel‐Cox log‐rank test was used in q. ***, P < 0.001, **, P < 0.01, *, P < 0.05. Scale bar = 1 mm (c,h), 50 µm (j), 100 µm (m).