Lysine specific demethylase (LSD1) as diagnosis and treatment target of myocardial hypertrophy and application
A demethylase and myocardial hypertrophy technology, applied in the directions of oxidoreductase, biochemical equipment and methods, medical preparations containing active ingredients, etc. any reports, etc.
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Embodiment 1
[0034] Histone demethylase inhibitors can induce cardiac hypertrophy experiments
[0035] SD rats (140-180g) were divided into three groups: control group, isoproterenol group (ISO), LSD1 inhibition group (OG-L002, Selleckchem), 8 rats in each group. The isoproterenol group was injected intraperitoneally with isoproterenol 2 mg / kg per day; the LSD1 inhibitor group was injected with OG-L00 250 μg / kg per day; the control group was injected with the same volume of normal saline.
[0036] Among them, the chemical structural formula of OG-L002 is as follows:
[0037]
[0038] Three weeks after administration, the SD rats were sacrificed, and their hearts were taken.
[0039] refer to figure 1 and figure 2 The experimental results can be seen: the schematic diagram of heart volume detection is as follows figure 1 , where, left → right: control group; isoproterenol group (ISO); OG-L002 group, the heart volume of isoproterenol group and OG-L002 group increased significantly; ...
Embodiment 2
[0047] Coarctation of the aorta refers to narrowing of the aorta in the region of the ductus arteriosus or ligamentum arteriosus. It is a common method for the commonly used mouse and rat cardiac hypertrophy models. In this example, aortic arch coarctation was used to construct a cardiac hypertrophy model in SD rats, and the effects of histone LSD1, H3K4 and H3K9 methylation levels were observed.
[0048] SD rats (140-180g) were divided into four groups: control group, sham operation group (Sham), aortic arch ligation operation group (TAC), 8 rats in each group. The myocardial hypertrophy model was successfully established in the aortic arch ligation group, see Figure 6 and Figure 7 .
[0049] From the experimental results, it can be seen that the ligation of the aortic arch successfully led to a larger heart size and an increase in the expression of hypertrophic factors, indicating that this method successfully established a cardiac hypertrophy model, see Figure 6 and ...
Embodiment 3
[0052] From the following experiments and results, it was found that overexpression of histone demethylase LSD1 can attenuate isoproterenol-induced cardiac hypertrophy.
[0053] SD rats (140-180g) were divided into four groups: control group, virus empty group (pEF1a), LSD1 overexpression virus group (pEF1a-LSD1), isoproterenol+LSD1 overexpression virus group (ISO+pEF1a- LSD1), 8 rats in each group.
[0054] The isoproterenol group was injected intraperitoneally with 2 mg / kg isoproterenol every day; the control group was injected with the same volume of normal saline. LSD1 overexpression lentivirus was packaged, concentrated by ultracentrifugation and injected directly into the myocardium in situ. At the same time, intraperitoneal injection of isoproterenol (ISO) was given, and samples were collected 3 weeks later. Using Western Blot to detect the protein expression level of LSD1, it was found that the experiment successfully achieved the overexpression of LSD1 protein level ...
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