Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip

Abstract

In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity. Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ± 9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models. Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant. Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.

Serum cytokines levels in patients with myocardial infarction with non-obstructive and obstructive coronary arteries

“…CCL-15 является провоспалительным хемокином, который ускоряет рекрутирование макрофагов в бляшки, усиливает продукцию металлопротеазы-9 из макрофагов и тем самым ускоряет дестабилизацию и разрыв фиброзной покрышки бляшки [19,20]. С учетом большего повышения CCL-15 у пациентов ИМБОКА в сравнении с контрольной группой, он может способствовать прогрессированию воспале-ния и дестабилизации бляшки у этой группы больных.…”

The Effects of FABP4 on Cardiovascular Disease in the Aging Population

“…In 681 patients with prevalent CVD, FABP4 was associated with cardiovascular death even after correction for confounders [ 58 ]. In a South African study involving black and white participants FABP4 was measured using the multiplex PEA technique and correlated to several phenotypes of vascular health [ 59 ]. FABP4 was associated with cIMT and pulse wave velocity, a marker of arterial stiffness and an independent predictor of cardiovascular risk, but not hypertension [ 59 ].…”

Precision medicine in secondary prevention of ischemic stroke: how may blood-based biomarkers help in clinical routine? An expert opinion

“…Promising biomarkers of inflammation associated with a higher risk of ischemic stroke include cytokines like IL-1, TNF-alpha, and IL-6, participating in a central immune pathway leading to hepatic production of several acute phase proteins, such as hsCRP, fibrinogen, plasminogen activator inhibitor, and serum amyloid A, which are themselves further possible biomarker of inflammation in ischemic stroke patients [22]. Other proteins involved in several inflammation pathways have been linked to higher risk of atherogenesis, such as the adhesion molecules ICAM-1 and VCAM-1, P-selectin, carboxypeptidase A1 and B1, Chemokine ligand 15, CXC ligand 16, tissue plasminogen activator, transferrin receptor protein to mention some [23][24][25].…”