Effects Of ω-3 Polyunsatuarated Fatty Acids On The Serum Lipid Levels, Inflammation Factors Of Patients And The Action Potential And Transient Outward Current Of Rat Ventricular Myocytes

Objective: To compare the effects ofω-3 polyunsatuarated fattyacids (ω-3 PUFAs) and atorvastatin(A) on the serum lipid levels, CD40s,soluble CD40 ligands (sCD40L) and highsensitive C-reactive protein(HsCRP) of patients with hyperlipidemia and acute coronarysyndrome(ACS) respectively. And also To investigate effects the onaction potential (AP) and transient outward current (I_to) of rat ventricularmyocytes by docosahexaenoic acid.Methods: (1)Sixty two patients with hyperlipidemia were randomlydivided into two groups, treated with 10 mg/d atorvastatin or 3g/d fishoil for 8 weeks. And their serum levels of lipid, sCD40L and HsCRPwere measured respectively at baseline (0 week) and after being treatedwith atorvastatin or fish oil for 4 weeks and 8 weeks. CD40s wereseparated by flow cytometry at the same time. 34 normal control subjectswere also investigated (just 0 week). (2) Patients with ACS wererandomly divided into two groups, treated with 3g/d fish oil and 10 mg/datorvastatin or 10 mg/d atorvastatin for 2 weeks. Their serum levels oftriglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C),apolipoprotein A₁ (ApoA₁), apolipoprotein B₁₀₀(ApoB₁₀₀), CD40s,sCD40Ls and HsCRP were investigated at baseline(0 week) and afterbeing treated with fish oil and atorvastatin or atorvastatin for 1 weeks and2 weeks. Sixty-one patients finished the study. (3) Studied the acuteeffects of docosahexaenoic acid (DHA) on AP and ,Ito recorded bywhole-cell patch clamp techniques in adult rat ventricular myocytesisolated by enzyme digestion.Results: 1.ω-3 polyunsatuarated fatty acids on the serum lipid levels,CD40/sCD40L and highsentive C-reactive .protein of patients withhyperlipidemia: (1) Compared with control, CD40s and sCD40Ls ofpatients with hyperlipidemia were significantly increased (P＜0.05);(2) Just after 4 weeks sCD40Ls were decreased remarkably in bothgroups [F: (4.80±1.36), (2.45±0.99) ng/ml; A: (4.55±1.23), (1.96±0.95)ng/ml; (P＜0.01)]. The levels of CD40 were fallen and there werestatistical significance only in F group after 8. weeks, from (9.97±5.46) to(7.48±3.12)% (P＜0.05), however, HsCRP levels were not changed beforeand after treatment; (3) After 8 weeks of treatment, TG were remarkablydecreased in both groups [F:(2.74±1.90), (1.78±0.88)mmol/l; A:(2.47±1.57), (1.66±1.10) mmol/l; P＜0.05] compared with baseline. TCand LDL-C were notably reduced only in A group [TC:(6.46±0.90),(4.79±1.20) mmol/L; LDL-C:(3.86±0.87), (2.52±0.77) mmol/; P＜0.001]. 2. Effects ofω-3 polyunsatuarated fatty acids combined, withatorvastatin on serum lipid levels, CD40/sCD40L and highsentivieC-reactive protein in patients with acute coronary syndrome: (1)Therewere significant reductions of TC, LDL-C and CD40 in both groups after2 weeks. In. F+A group, TC was decreased from (4.02±1.06) to(3.21±0.98)mmol/l(P＜0.01), LDL-C was reduced from (2.53±0.93) to(1.91±0.76)mmol/l (P＜0.01), and CD40 was fallen from (9.26±4.48) to(6.01±3.54)% (P＜0.05). In A group, TC, LDL-C and CD40 were alsodecreased remarkably [(4.49±0.99), (3.84±1.18)mmol/l; (2.86±1.02),(2.31±1.08) retool/l; (9.90±5.19), (6.96±3.17)%; (P＜0.05)]. But HsCRP,TG and sCD40L reduction were all not significant. (2) In the F+A group,TC, LDL-C and HsCRP were decreased to a greater extent compared withA group. (3) No correlation was found between CD40 and HsCRP, TC orLDL-C.3. Effects on the action potential and transient outward current of ratventricular myocytes by docosahexaenoic acid: (1) Low concentrations ofDHA (＜20μmol/L) could inhibit I_to, but not prolong AP durations(APDs) significantly; (2)Higher concentrations of DHA (30-200μmol/L)further decreased I_to and prolonged the APD, which was more significantwith increase of DHA concentrations; (3) APDs were prolonged within 5minutes after DHA with different concentrations was added. I_to wasdecreased within 10 minutes after DHA was added, however, it remained stable after 10 minutes.Conclusion: Hyperlipidemia stimulates upregulation ofCD40/sCD4OL,ω-3 polyunsatuarated fatty acids (ω-3PUFAs) andatorvastatin not only has the property of lowering lipid but also caninhibit the CD40/sCD40L system, which may contribute to theiranti-inflammatory and anti-atherogenic activity,ω-3PUFAs combinedatorvastatin therapy significantly reduced plasma lipid and HsCRP levelsmore than atorvastatin alone,ω-3 PUFAs could enhance the lipid-lowingand antiinflammation effects of atorvastatin. DHA not only inhibits I_to butalso remarkablely prolonges the APD, which may contribute to itsantiarrythmatic activity.