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

Abstract

BackgroundThe 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.MethodsAltogether 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.ResultsHypertension, 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 (r s = 0.271; r s = 0.476), between HIF-1α and LDL-C (r s = 0.077; r s = 0.470), as well as between HO-1 and CysC (r s = 0.492; r s = 0.190) or hs-CRP (r s = 0.569; r s = 0.542) (all P < 0.05). MAPK-1, HIF-1α and HO-1 were also, respectively, positively correlated with CysC (r s = 0.415), hs-CRP (r s = 0.137), and TG (r s = 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).ConclusionsExpressions of p38MAPK-1, HIF-1 and HO-1 could serve as predictive roles for coronary lesions among peri-menopausal women.

Correlation between genetic polymorphisms within the MAPK1/HIF‐1/HO‐1 signaling pathway and risk or prognosis of perimenopausal coronary artery disease

“…Participants were included in the CAD group if ≥1 of their arteries had >50%‐diameter stenosis . Lesions of CAD patients were classified as single‐, double‐, and triple‐vessel lesions based on the amount of stenosed coronary vessel.…”

“…The Gensini score was used to evaluate the degree of coronary artery stenosis . Specifically, the scoring was applied as follows: (1) score of 1 when the proportion of stenosis was ≤25%; (2) score of 2 when the proportion of stenosis was 25% to 50%; (3) score of 4 when the proportion of stenosis was 50% to 75%; (4) score of 8 when the proportion of stenosis was 75% to 90%; (5) score of 16 when the proportion of stenosis was 90% to 99%; and (6) score of 32 when the proportion of stenosis was 100%.…”

“…Participants were included in the CAD group if ≥1 of their arteries had >50%-diameter stenosis. 20 Lesions of CAD patients were classified as single-, double-, and triple-vessel lesions based on the amount of stenosed coronary vessel. The classification (type A, type B, and type C) regarding complexity of the CAD lesions was made in accordance with the principles of the American College of Cardiography/ American Heart Association.…”

“…The Gensini score was used to evaluate the degree of coronary artery stenosis. 20 Specifically, the scoring was applied as follows: (1) score of 1 when the proportion of stenosis was ≤25%; (2) score of 2 when the proportion of stenosis was 25% to 50%; (3) score of 4 when the proportion of stenosis was 50% to 75%; (4) score of 8 when the proportion of stenosis was 75% to 90%; (5) score of 16 when the proportion of stenosis was 90% to 99%; and (6) score of 32 when the proportion of stenosis was 100%. The coefficients for different segments of the coronary arteries were as follows: left main coronary artery (×5), the proximal left anterior descending branch (×2.5), left anterior descending branch in the middle (×1.5), far-left anterior descending branch (×1), the first diagonal branch (×1), the second diagonal branch (×0.5), and the proximal left circumflex branch (×2.5).…”

Protein kinase D1 regulates hypoxic metabolism through HIF-1α and glycolytic enzymes incancer cells

“…Hypoxia not only induces the expression of HIF-1α, but also increases the phosphorylation and activation of p38 MAPK in cancer cells (51). The activation of p38 MAPK signaling is necessary for HIF-1α accumulation and nuclear translocation (52). In the present study, we observed that the knockdown and overexpression of PKD1 elevated the expression of p-p38 MAPK in order to further ascertain whether p-p38 MAPK is involved in the regulation of PKD1 in hypoxia.…”