The complement system in human cardiometabolic disease

Complement Component 3 Is Associated with Metabolic Comorbidities in Older HIV-Positive Adults

“…C3 is primarily produced by hepatocytes but is also produced by adipocytes as an adipokine; in the setting of obesity, higher C3 levels are associated with a low-level systemic inflammatory state and are hypothesized to contribute to the development of insulin resistance, though the exact causal mechanisms remain unclear. [10][11][12][13][14][15] Higher C3 is also associated with nonalcoholic fatty liver disease, the primary liver manifestation of MetS, and may contribute to the impaired liver function and dyslipidemia observed in cardiometabolic disease. 16,17 The complement system has been hypothesized to play a role in the development of MetS and may be involved in deranged postprandial lipid metabolism in this setting.…”

The Complement System in Hemodialysis Patients: Getting to the Heart of the Matter

“…Uncontrolled activation of the complement system can result in renal and systemic diseases including atypical hemolytic uremic syndrome (aHUS) [7] and membranoproliferative glomerulonephritis [8]. Furthermore, deregulations in the complement system have also been linked with endothelial dysfunction, atherosclerosis, and impaired coagulation [9]. Of interest, several studies in non-renal patients have shown associations between complement components and cardiovascular disease.…”

“…Similarly, the downstream component C5a has been associated with cardiovascular disease in patients with advanced atherosclerosis [20]. Although these data come from a limited number of studies performed in generally small cohorts, and reported data have not always been consistent [9], these findings do warrant further investigation of the role of the complement system in patients with advanced chronic kidney disease.…”

Cardiovascular Disease and NASH

“…The complement system may be involved in all these processes based on its immune, inflammatory and metabolic functions. 18 Furthermore, systemic complement levels may be involved in coagulation and fibrinolysis, which together with endothelial dysfunction and atherosclerosis result in cardiovascular disease. 18 The complement-C3 has shown independent associations with insulin resistance, liver dysfunction and in the risk of MetS and T2DM.…”

“…18 Furthermore, systemic complement levels may be involved in coagulation and fibrinolysis, which together with endothelial dysfunction and atherosclerosis result in cardiovascular disease. 18 The complement-C3 has shown independent associations with insulin resistance, liver dysfunction and in the risk of MetS and T2DM. 19,20 Circulating levels of several inflammatory markers (Creactive protein, interleukin-6, monocyte chemotactic protein 1, and TNF-a), procoagulant factors (plasminogen activator inhibitor 1, fibrinogen, and factor VII), and oxidative stress markers are highest in patients with NASH independent of obesity and other potentially confounding factors.…”