Atrial APD prolongation caused by the upregulation of RAGE and subsequent INaL increase in diabetic patients

Figures

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  Figure 1 Comparison of APD in the left atrial cells of patients without diabetes mellitus and those with diabetes mellitus (A,B) Representative traces of APDs. (C,D) Statistical analysis of APD50 and APD90. (E) Resting membrane potential. (F) Overshoot. Non-DM, nondiabetic mellitus; DM, diabetes mellitus. n = 7–8 cells from 10 patients in the Non-DM and DM groups. Data are expressed as the mean ± SEM. *P < 0.05 vs Non-DM, by t tests.

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  Figure 2 Comparison of the I NaL in isolated atrial myocytes of nondiabetic and diabetic patients (A–C) Representative traces of INaL. (D) Current density of INaL. Non-DM, nondiabetic mellitus; DM, diabetes mellitus. n = 7–8 cells from 10 patients in the Non-DM and DM groups. Data are expressed as the mean ± SEM. *P < 0.05 vs Non-DM, according to t tests.

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  Figure 3 Expression of RAGE in the atria of diabetic patients and HL-1 cells treated with HG (A) Western blot analysis of RAGE expression in atrial tissues from diabetic and nondiabetic patients. n = 4. *P < 0.05 vs Non-DM; P values were determined via an unpaired t test. (B) The expression of RAGE in atrial tissues from diabetic patients and nondiabetic patients, as determined by immunofluorescence staining. n = 3. The tissues were stained with an anti-RAGE antibody, and the nuclei were stained with DAPI (blue). (C) Western blot analysis of RAGE expression in NG- and HG-treated HL-1 cells. n = 3. *P < 0.05 vs NG; P values were determined via an unpaired t test. (D) qRT-PCR analysis of SCN10A mRNA expression in NG and HG HL-1 cells. n = 3. ***P < 0.001 vs NG. P values were determined via an unpaired t test. Non-DM, nondiabetic mellitus; DM, diabetes mellitus; HG, high glucose; NG, normal glucose.

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  Figure 4 Effects of RAGE knockdown on the APD in HG-treated HL-1 cells (A) Representative APD traces recorded at 1 Hz from cells incubated with normal glucose (NG, 5.5 mM glucose), HG (33 mM glucose), HG + NC (33 mM glucose with NC) or HG + Si-RAGE (33 mM glucose with Si-RAGE). (B,C) Averaged AP duration (APD) at 50% and 90% repolarization levels in various groups, n = 3. (D) Resting membrane potential, n = 3. (E) Overshoot, n = 3. NG, normal glucose; HG, high glucose; NC, negative control sequence for RAGE; Si-RAGE, RAGE siRNA. Data are expressed as the mean ± SEM. ***P < 0.001 vs the NG group; #P < 0.05, ##P < 0.01 vs the HG + NC group; t tests were performed.

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  Figure 5 Effects of RAGE knockdown on the I NaL of HG-treated HL-1 cells (A–C) Representative traces of INaL recorded at 1 Hz, 2 Hz and 8 Hz in NG, HG, HG + NC or HG + Si-RAGE cells. n = 7. (D) Current density of INaL. n = 7. NG, normal glucose; HG, high glucose; NC, negative control sequence for RAGE; Si-RAGE, RAGE siRNA. Data are expressed as the mean ± SEM. *P < 0.05 vs NG; #P < 0.05 vs the HG + NC group, as determined by t tests.