PMID- 34362270 OWN - NLM STAT- MEDLINE DCOM- 20220920 LR - 20231031 IS - 1708-539X (Electronic) IS - 1708-5381 (Linking) VI - 30 IP - 5 DP - 2022 Oct TI - The protective mechanism of folic acid on hyperhomocysteinemia-related arterial injury in spontaneously hypertensive rats: Folic acid against arterial inflammation. PG - 988-998 LID - 10.1177/17085381211036549 [doi] AB - BACKGROUND: Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. Studies found that folic acid (FA) supplementation can reduce the risk of cardiovascular and cerebrovascular events. The aim of the present study was to explore the potential mechanisms of FA attenuating HHcy-related arterial injury in spontaneously hypertensive rats (SHRs). METHODS: 24 SHRs were randomized into the control group, the HHcy group, and the HHcy + FA group (8 per group). The SHRs in the HHcy group and the HHcy + FA group were given DL-Hcy intraperitoneally to mimic hypertension associated with HHcy. The SHRs in the HHcy + FA group were given FA by gavage to mimic an FA-fortified diet. The histopathology and immunohistochemistry of rat aorta and carotid artery were analyzed, and the relative expression levels of immune/inflammation and oxidative stress molecules in arterial tissue were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: FA significantly reduced the expression levels of nuclear factor-kappa-gene binding (NF-kappaB) p65/Rela and interleukin-6 (IL-6) in rat arterial tissues, as well as the levels of plasma HHcy and serum malondialdehyde (MDA) in hypertension associated with HHcy rats (p < 0.05). At the same time, FA significantly increased the serum superoxide dismutase (SOD) level in hypertension associated with HHcy rats, and even the SOD level of the HHcy + FA group was higher than that of the control group (p < 0.05). However, HHcy induced the opposite results of the above indicators in SHRs compared with the control group (p < 0.05). CONCLUSIONS: The arterial protection mechanisms of FA are related to reducing the concentration of HHcy to eliminate the tissue toxicity of HHcy, inhibiting NF-kappaBp65/Rela/IL-6 pathway molecules to regulate inflammatory response, and promoting the potential anti-oxidative stress pathway molecules to reduce oxidative stress level. FAU - Zhang, Lihua AU - Zhang L AD - Shandong Provincial Qianfoshan Hospital, 74738Shandong University, Jinan, Shandong, China. AD - Department of Medicine, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, China. FAU - Li, Zhongliang AU - Li Z AD - Department of Women Healthcare, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, China. FAU - Xing, Changcheng AU - Xing C AD - 74738Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Ma, Xiaoshan AU - Ma X AD - Department of Medicine, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, China. FAU - Xu, Rui AU - Xu R AUID- ORCID: 0000-0002-6212-707X AD - Shandong Provincial Qianfoshan Hospital, 74738Shandong University, Jinan, Shandong, China. AD - Department of Cardiology, 74738The First Affiliated Hospital of Shandong First Medical University, Jinan, China. LA - eng PT - Journal Article DEP - 20210806 PL - England TA - Vascular JT - Vascular JID - 101196722 RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 4Y8F71G49Q (Malondialdehyde) RN - 935E97BOY8 (Folic Acid) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Animals MH - *Arteritis/complications MH - Folic Acid/pharmacology MH - *Hyperhomocysteinemia/complications/drug therapy MH - *Hypertension/complications/drug therapy MH - Interleukin-6 MH - Malondialdehyde/metabolism MH - NF-kappa B MH - Rats MH - Rats, Inbred SHR MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Folic acid OT - NADPH oxidase OT - NF-kappaB OT - hypertension associated with hyperhomocysteinemia OT - immune/inflammation OT - oxidative stress EDAT- 2021/08/08 06:00 MHDA- 2022/09/21 06:00 CRDT- 2021/08/07 05:22 PHST- 2021/08/08 06:00 [pubmed] PHST- 2022/09/21 06:00 [medline] PHST- 2021/08/07 05:22 [entrez] AID - 10.1177/17085381211036549 [doi] PST - ppublish SO - Vascular. 2022 Oct;30(5):988-998. doi: 10.1177/17085381211036549. Epub 2021 Aug 6.