Table 1.
Variable biomarkers in PE
| Biomarker | Levels in PE | Measurement Source | Biological Functions | References | |
|---|---|---|---|---|---|
| 1 | sFlt-1 | Increased | Serum; toward end of pregnancy | sFLT-1 binds to free VEGF and PlGF in the maternal circulation, thus reducing their bioavailability for their membrane receptor. | (125, 126) |
| 2 | HIF-1α | Increased | Serum—1st and 2nd trimester | Transcription factor that controls responses to hypoxia, mediating angiogenesis, cell migration, and immune function; also, stimulates sFLT-1 production in trophoblast. | (127, 128) |
| 3 | O2•−, OH• and H2O2 | Increased | Serum—early pregnancy | Causes oxidative damage. | (104) |
| 5 | DCF, reactive nitric oxide metabolites ( and ) | Increased | Serum—early pregnancy | Found in placental mitochondria; this suggests that the primary source of ROS contributing to oxidative stress is mitochondria. | (129, 130) |
| 7 | AT1-AA | Increased | Serum—early pregnancy until nearly 18 mo following postpartum | Bind and activate AT1 receptors to increase angiotensin II sensitivity and increase concentration of endothelin-1, sFLT-1, and ROS, which affect renal function. | (131–135) |
| 8 | sEng | Increased | Serum—from 20–23 wk to 27–30 wk of gestation, and then rapidly increases at 36–38 wk | An antiangiogenic protein that binds to TGF-β1, preventing its interaction with its natural angiogenic receptor, thereby inhibiting TGF-β1-induced eNOS activation and vasodilation (NO-mediated vasodilation). | (3, 136–138) |
| 9 | Inhibin A | Increased | Serum—from 4th wk of gestation | Associated with hypoxia and shows significant elevation by 10 wk of pregnancy. It downregulates activin-A signaling, which enhances extravillous trophoblast migration. This characteristic could potentially aid in the early diagnosis of preeclampsia. | (139–141) |
| 11 | Activin A | Increased | Serum—late 2nd and 3rd trimester | Glycoprotein growth factor involved in cellular differentiation and proliferation. Its levels correlate with cardiac global longitudinal strain. | (139) |
| 11 | VEGF, PlGF | Decreased | Serum—1st trimester | Regulates endothelial cell proliferation, angiogenesis, and vascular permeability. Low-circulating PlGF as a biomarker for poor placental function and a mediator of the angiogenic switch. | (142, 143) |
| 12 | Homocysteine | Increased | Serum—16th wk of gestation to delivery | Elevated levels of homocysteine are observed because of the loss of NO-mediated vasodilation, which is characteristic of oxidative inactivation of the NO synthase cofactor. | (105, 144, 145) |
| 14 | TNF-α, IL-6, IL-17, IL-2, IFN-γ, ICAM-1, VCAM-1, TLR-9 | Increased | Serum—early to midpregnancy | Proinflammatory cytokines. | (146, 147) |
| 15 | SOD, CAT, GPx, selenium, Co-Q10 | Decreased | Serum | Enzymatic antioxidants that promote the conversion of ROS into harmless products. | (23, 113, 148–150) |
| 16 | Thiols in plasma, α-tocopherol, Zinc and Lycopene, Vitamin A, C and E, fatty acids Docosahexaenoic acid | Decreased | Serum | Nonenzymatic antioxidants. | (113, 149, 151) |
| 17 | BNP, ANP, cTnI | Increased | Serum—after 20 wk till 3–6 wk postpartum | Indicators of myocardial strain that are released with the stretching of ventricles. | (13, 152–158) |
AT1-AA, angiotensin II type 1 receptor agonistic autoantibody; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; CAT, catalase; CLPP, caseinolytic peptidase P; Co-Q10, coenzyme Q10; cTnI, cardiac troponin I; DCF, dichlorofluorescein; DHA, docosahexaenoic acid; eNOS, endothelial nitric oxide synthase; GPx, glutathione peroxidase; HIF-α, hypoxia-inducible factor α; H2O2, hydrogen peroxide; ICAM-1, intercellular adhesion molecule-1; IFN-γ, interferon-γ; IL-2, interleukin-2; IL-6, interleukin-6; IL-17, interleukin-17; LDL, low-density lipoproteins; LDL-C, low-density lipoprotein-cholesterol; mtROS, mitochondrial ROS; NK, natural killer cells; NO, nitric oxide; O2•−, superoxide; OH•, hydroxyl radicals; PAPP-A, pregnancy-associated plasma protein-A; PE, preeclampsia; PlGF, placental growth factor; ROS, reactive oxygen species; sEng, soluble endoglin; sFLT-1, soluble fms-like tyrosine kinase-1; SOD, superoxide dismutase; TC, total cholesterol; TGs, triglycerides; TGF-β1, transforming growth factor β1; TLR-9, Toll-like receptors; TNF-α, tumor necrosis factor-α; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.