Associations of proteins relevant to MAPK signaling pathway (p38MAPK-1,HIF-1 and HO-1) with coronary lesion characteristics and prognosis of peri-menopausal women.
BACKGROUND
The present study was intended to explore whether three proteins within MAPK signaling pathway (i.e. p38MAPK-1, HIF-1 and HO-1) were correlated with peri-menopausal women's coronary lesion features and prognosis.


METHODS
Altogether 1449 peri-menopausal women were divided into non-coronary artery disease (CAD) group (n = 860) and CAD group (n = 589), including 167 pre-menopausal CAD populations and 422 post-menopausal CAD populations. General information about CAD risk parameters were gathered, including age, family history of CAD or hypertension or diabetes mellitus, bilirubin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and so on. Coronary angiography results were judged, and CAD score was calculated with application of Genisin scoring method. Besides, detection of MAPK-1 levels was implemented with Strept Avidin-Biotin Complex (SABC) method, while HIF-1 and HO-1 expressions in the serum were determined utilizing ELISA detection kit. Correlations among protein expressions, characteristics of coronary lesions and prognosis of CAD populations were finally evaluated.


RESULTS
Hypertension, hyperlipoidemia, diabetes and smoking history were more prevalent among postmenopausal CAD women than premenopausal CAD women (P < 0.05). Furthermore, postmenopausal women seemed to be significantly associated with multiple (i.e. double and triple) vessel lesions and severe lesion types (type B and C), when compared with premenopausal CAD group (P < 0.05). Similarly, remarkably elevated expressions of p38MAPK-1, HIF-1 and HO-1 were found within postmenopausal CAD populations in comparison to premenopausal ones (P < 0.05). The internal CysC, hs-CRP, TG and LDL-C concentrations all accorded with the following tendency: postmenopausal CAD women > premenopausal CAD women > non-CAD women. Moreover, p38MAPK-1, HIF-1 and HO-1 expressions were up-regulated with increasing number of vessel lesions and severity of coronary lesions among peri-menopausal women. Besides, among both pre-menopausal and post-menopausal CAD groups, positive correlations could be observed between MAPK-1 and TG (rs= 0.271; rs= 0.476), between HIF-1α and LDL-C (rs= 0.077; rs= 0.470), as well as between HO-1 and CysC (rs= 0.492; rs= 0.190) or hs-CRP (rs= 0.569; rs= 0.542) (all P < 0.05). MAPK-1, HIF-1α and HO-1 were also, respectively, positively correlated with CysC (rs= 0.415), hs-CRP (rs= 0.137), and TG (rs= 0.142), regarding post-menopausal CAD women (all P < 0.05). Finally, only SBP and TG were regarded as independent risk factors for CAD prognosis (i.e. high Genisin score) among premenopausal women (OR = 1.02, 95%CI: 1.01-1.18, P = 0.043; OR = 1.82, 95%CI: 1.01-3.33, P = 0.047).


CONCLUSIONS
Expressions of p38MAPK-1, HIF-1 and HO-1 could serve as predictive roles for coronary lesions among peri-menopausal women.
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Liqiu
L
Yan
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China. c_xufen@163.com.
Xufen
X
Cao
Department of Gynecology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, 061001, Hebei Province, China.
Saitian
S
Zeng
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Zhe
Z
Li
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Zheng
Z
Lian
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Jiawang
J
Wang
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Fengfeng
F
Lv
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Yunfei
Y
Wang
Department of Cardiology, Cangzhou Central Hospital, Hebei Medical University, No. 16 Xinhua West Road, Cangzhou, Hebei Province, 061001, China.
Yanshen
Y
Li
D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases
Coronary lesion characteristics; HIF-1; HO-1; Perimenopausal CAD; Prognosis; p38MAPK-1