Antibodies against Angiotensin II Type 1 and Endothelin 1 Type A Receptors in Cardiovascular Pathologies

Angiotensin II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) are G-protein-coupled receptors (GPCRs) expressed on the surface of a great variety of cells: immune cells, vascular smooth cells, endothelial cells, and fibroblasts express ETAR and AT1R, which are activated by endothelin 1 (ET1) and angiotensin II (AngII), respectively. Certain autoantibodies are specific for these receptors and can regulate their function, thus being known as functional autoantibodies. The function of these antibodies is similar to that of natural ligands, and it involves not only vasoconstriction, but also the secretion of proinflammatory cytokines (such as interleukin-6 (IL6), IL8 and TNF-α), collagen production by fibroblasts, and reactive oxygen species (ROS) release by fibroblasts and neutrophils. The role of autoantibodies against AT1R and ETAR (AT1R-AAs and ETAR-AAs, respectively) is well described in the pathogenesis of many medical conditions (e.g., systemic sclerosis (SSc) and SSc-associated pulmonary hypertension, cystic fibrosis, and allograft dysfunction), but their implications in cardiovascular diseases are still unclear. This review summarizes the current evidence regarding the effects of AT1R-AAs and ETAR-AAs in cardiovascular pathologies, highlighting their roles in heart transplantation and mechanical circulatory support, preeclampsia, and acute coronary syndromes.

Chronic Cognitive and Cerebrovascular Function Following Mild Traumatic Brain Injury in Rats

Severe traumatic brain injury results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (N=20) or sham (N=21). Cognitive function was assessed (3- and 6-month novel object recognition (NOR), novel object location (NOL) and temporal order object recognition (TOR)). 6-month cerebral blood flow (CBF) and blood volume (CBV) using contrast MRI and ex vivo pial artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed impaired NOR, with similar (non-significant) trends in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus and primary somatosensory barrel cortex while inversely correlating with arterial smooth muscle-dependent dilation. 6-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin II stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin II-stimulated smooth muscle-dependent vasoreactivity, a paradigm that could advance understanding of the long-term sequelae of human mild TBI.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers and Mortality in Patients with Hypertension Hospitalized with COVID-19

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are common hypertension medications. We aimed to investigate the association between treatment with ACEIs/ARBs and disease severity and mortality in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19). Methods: Information from the medical records of 180 hospitalized patients diagnosed with COVID-19 infection admitted in 2020 to Loghman Hakim Hospital, Tehran, Iran, was collected. Clinical histories, drug therapies, radiological findings, hospital courses, and outcomes were analyzed in all the patients. The demographic and clinical characteristics of the patients were also analyzed, and the percentage of patients with hypertension taking ACEIs/ARBs was compared between survivors and nonsurvivors. Results: The study population consisted of 180 patients at mean±SD age of 67.76±18.72 years. Hypertension was reported in 72 patients (40.0%). Patients with hypertension were older than those without it (mean±SD age =72.35±12.09 y). Among those with hypertension, death occurred in 33 patients (45.8%), of whom 60.6% were men. Fifty-three patients (73.6%) with hypertension were on ACEIs/ARBs. The ACEIs/ARBs group had a significantly lower mortality rate than the non-ACEIs/ARBs group (37.7% vs 68.4%; OR: 0.192; 95% CI: 0.05–0.68; P=0.011). Conclusion: This single-center study found no harmful effects associated with ACEIs/ARBs treatment. Patients on ACEIs/ARBs had a lower rate of mortality and disease severity than the non-ACEIs/ARBs group. Our study supports the current guideline to continue ACEIs/ARBs in patients with hypertension.