Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway.
Yu An LuYunfei JiangHye-Won YangJin HwangYung Hyun ChoiBo-Mi RyuPublished in: International journal of molecular sciences (2021)
Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.
Keyphrases
- vascular endothelial growth factor
- endothelial cells
- nitric oxide synthase
- pi k akt
- nitric oxide
- signaling pathway
- poor prognosis
- cardiovascular disease
- cell proliferation
- high glucose
- metabolic syndrome
- binding protein
- type diabetes
- cell cycle arrest
- body mass index
- coronary artery disease
- subarachnoid hemorrhage
- blood brain barrier
- brain injury
- long non coding rna