Cardiac hypertrophy and the dynamic changes in structure and function after pressure overload
Introduction: Cardiac hypertrophy establishes itself when the heart has to pump against an increased resistance in the vasculature. Contrary to exercise-induced hypertrophy, pathological hypertrophy is characterized by an increased amount of interstitial collagen, induction of foetal-type genes, and an increased lumen size. It has been described that, following aortic banding, the γ isoform of p38MAPK translocates into the nucleus during the progression of cardiac hypertrophy, suggesting that this isoform of p38 may be involved in the synthesis of proteins involved in pathological remodelling (Dingar et al, 2010). Hypothesis: It was hypothesised that p38γδ knock out (KO) mice would display cardiac hypertrophy to a lesser extent than wild type (WT) mice. Methods: 10 WT and 10 p38γδKO mice underwent abdominal aortic banding surgery. By tying against a 28-gauge blunted needle, each animal was banded on the descending aorta using 8/0 nylon suture. Following surgery, animals were monitored over an 8 week period using high resolution cardiac ultrasound, to assess changes in cardiac function (at weeks 2, 4, 6 and 8). Results: Cardiac output (CO) increased from BL (WT: 22.51 ml/min; KO: 26.01 ml/min) to week 8 (WT: 29.81 ml/min; KO: 33.81 ml/min). Stroke volume (SV) followed a similar trend after an initial drop (BL: WT = 56.06 µl; KO = 47.36 µl vs. week 8: WT = 54.44 µl; KO = 62.62 µl). At the same time ejection fraction (EF) (BL: WT = 71.46 %; KO = 72.28 % vs. week 8: WT = 41.19 %; KO = 54.40 %) and fraction of shortening (FS) (BL: WT = 40.23 %; KO = 40.51 % vs. week 8: WT = 20.39 %; KO = 28.20 %) decreased significantly in WT over the course of the study. Pulmonary and aortic mean flow decreased, as did pulmonary velocity time integral (VTI), however aortic VTI remained constant. Discussion: From the analysis of the results it appears that KO mice were better protected against the development of pathological hypertrophy following pressure overload. This suggests strongly the involvement of p38γ or δ MAPK in the development of cardiac remodelling. Conclusion: Pharmacological inhibition of p38γ or δ MAPK may pose a potential new treatment avenue in the prevention of pathological cardiac hypertrophy. However, further research into the potential effects this might have on other organs in the body needs to be addressed first.
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