Anti-Aldosterone monoclonal antibody, clone A12/4215

Purpose of Review Preeclampsia and chronic kidney disease have a complex, bidirectional relationship. Women with kidney disease, with even mild reductions in glomerular filtrate rate, have an increased risk of developing preeclampsia. Preeclampsia, in turn, has been implicated in the subsequent development of albuminuria, chronic kidney disease, and end-stage kidney disease. We will discuss observational evidence and mechanisms linking the two disease processes. Recent Findings Preeclampsia is characterized by an imbalance in angiogenic factors that causes systemic endothelial dysfunction. Chronic kidney disease may predispose to the development of preeclampsia due to comorbid conditions, such as hypertension, but is also associated with impaired glycocalyx integrity and alterations in the complement and renin-angiotensin-aldosterone systems. Preeclampsia may lead to kidney disease by causing acute kidney injury, endothelial damage, and podocyte loss. Preeclampsia may be an important sex-specific risk factor for chronic kidney disease. Understanding how chronic kidney disease increases the risk of preeclampsia from a mechanistic standpoint may open the door to future biomarkers and therapeutics for all women.

The excessive activation of renin-angiotensin system (RAS) is one of key pathophysiological characteristics in the development of cardiac remodelling. Angiotensin (Ang) II, as a main active peptide in RAS, induces cardiac structural disorders and dysfunction. However, the molecular mechanisms are still not fully disclosed. Present study aimed to determine the role and potential mechanisms of cardiac TIR-domain-containing adapter-inducing interferon-beta(TRIF) in Ang-II-mediated cardiac remodelling in mice. In vitro and in vivo studies showed Ang II and downstream aldosterone obviously increased the expression of TRIF, accompanied with cardiac structural abnormalities and functional injuries. Specific blockage of cardiac TRIF effectively decreased Ang-II/aldosterone-induced cardiac inflammation, fibrosis, hypertrophy and dysfunction in mice. Mechanistically, the TRIF triggered the activation of EGF receptor (EGFR) signalling by nuclear factor (NF)-kappa B transcriptional regulation and downstream EGFR ligands. Taken together, present study supported that cardiac TRIF was a potential therapeutic target for attenuating cardiac pathophysiological remodelling. The TRIF/EGFR axis partially explained the molecular mechanism of Ang-II/aldosterone-induced cardiac inflammation, fibrosis, hypertrophy and dysfunction in mice.