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Exercise, but not statins improve endothelial function in obese rats

Session Young Investigator Award 3 - Secondary prevention and rehabilitation Section

Speaker Ines Urbaneck

Event : ESC Preventive Cardiology (Formerly EuroPrevent) 2019

  • Topic : basic science
  • Sub-topic : Cardiac Diseases
  • Session type : Young Investigator Award Abstracts

Authors : I Urbaneck (Greifswald,DE), F Lorenz (Greifswald,DE), I Materzok (Greifswald,DE), L Maletzki (Greifswald,DE), SB Felix (Greifswald,DE), R Busch (Greifswald,DE), M Doerr (Greifswald,DE), M Bahls (Greifswald,DE)

Authors:
I Urbaneck1 , F Lorenz1 , I Materzok1 , L Maletzki1 , SB Felix1 , R Busch1 , M Doerr1 , M Bahls1 , 1University Medicine of Greifswald, Internal Medicine B - Greifswald - Germany ,

Topic(s):
Basic Science - Cardiac Diseases

Introduction

Statins and exercise training (ET) improve endothelial function. The mechanisms by which statins in combination with ET alter vascular function are largely unknown. We investigated how statins influence the effects of ET on vascular function in obese rats.

Methods

Eight-week-old male Wistar rats (n = 46) received a high-fat diet for 20 weeks. The rats were randomized after into four groups after eight weeks: sedentary (SED; n =11), exercise (EX; n=11), statin (STAT; n=13) and exercise with statin (EX/STAT; n=11). Simvastatin (10mg/d/kg) was administered in drinking water. The rats exercised for 12 weeks, 5 days/week for 1 h/day at 18 m/min. Endothelium-dependent (acetylcholine [Ach]) and – independent (sodium-nitroprusside [SNP]) vascular function was assessed in the abdominal aorta using in vitro myography. Gene expression and protein abundance of nitric-oxide soluble guanylate cyclase (NO-sGC) signaling was assessed using q-PCR and Western blot.

Results

Statin treatment significantly reduced cholesterol levels and did not influence exercise duration or intensity. ET independent of statins improved endothelium dependent vasodilation in EX and EX/STAT compared to SED and STAT, respectively. In untreated rats ET did not alter SNP vasodilation. However, in statin treated animals, ET improved SNP vasodilation. ET and statins increased NO protein abundance by 40% and 80%, respectively, compared to SED. However, in treated rats ET reduced NO to 40% above SED. Protein phosphatase 1 regulatory subunit 14A (CPI17), an inhibitor protein of smooth muscle myosin phosphatase showed a significant statin and exercise interaction at gene expression level (p < .0001). In untreated rats, ET upregulated CPI17 gene expression by 50% (p < .05). In treated rats a downregulation of 35% (p < .05) was observed. The results were similar on the protein level. The myosin phosphatase target subunit 1 (MYPT1) which drives the cGMP independent smooth muscle myosin phosphatase calcium desensitization was increased due to statin treatment (40%) and not affected by ET. Statin reduced sGCa protein content by more than 80%. Protein kinase cGMP-dependent 1 (PRKG1), which phosphorylates multiple targets implicated in modulating cellular calcium was significantly increased (50%; p < .05) in non-treated but decreased in treated rats. Protein abundance of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), which drives the uptake of calcium into the sarcoplasmic reticulum was reduced by statins (50%) and not rescued by ET.

Conclusion

ET independent of statin treatment improved endothelium-dependent vasodilation. Interestingly, in untreated animals these improvements were most likely driven by NO, while in animals receiving statins, ET altered vascular smooth muscle calcium handling and desensitization. Overall our results suggests that individuals receiving statins should exercise to maintain vascular health.

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