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Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition.

Sci Rep

January 2025

Department of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.

We previously demonstrated that the inability of primary endothelial cilia to sense fluid shear stress can lead to nitric oxide (NO) deficiency and cause hypertension (HTN). Decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in Alzheimer's disease (AD) patients through increased deposition of amyloid beta (Aβ). However, the molecular mechanisms underlying the pathogenesis of HTN and AD are incompletely understood.

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Severe pulmonary arterial hypertension and cardiogenic shock in acute systemic lupus erythematosus.

BMJ Case Rep

January 2025

Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.

We describe a woman in her late 20s with newly diagnosed systemic lupus erythematosus (SLE), who presented with fulminant pulmonary arterial hypertension (PAH) requiring inotropic and extracorporeal support. She was established on triple pulmonary vasodilator therapy with concurrent aggressive immunosuppression; however, treatment was complicated by infection and diffuse alveolar haemorrhage, necessitating delays in immunosuppression and withdrawal of epoprostenol. Despite this, with ongoing suppression of her SLE, her pulmonary haemodynamics improved, with normal pressures on right heart catheterisation several months later allowing stepdown to sildenafil monotherapy.

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The Circulating Renin-Angiotensin System and Mortality among Patients Hospitalized for COVID-19: A Mechanistic Substudy of the ACTIV-4 Host Tissue Trials.

Am J Physiol Lung Cell Mol Physiol

January 2025

Department of Internal Medicine, Section of Pulmonary, Critical Care, Allergy, and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

SARS-CoV-2 targets angiotensin converting enzyme-2 (ACE2), a key peptidase of the renin-angiotensin system (RAS), which regulates the balance of the vasoconstrictor/inflammatory peptide Ang II and the vasodilator/anti-inflammatory peptide Ang-(1-7). Few studies have quantified the circulating elements of the RAS longitudinally in SARS-CoV-2 infection and their association with COVID-19 outcomes. Thus, we evaluated the association of circulating RAS enzymes and peptides with mortality among patients with COVID-19.

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Objective: Carotid artery disease is a major cause of stroke for which the standard treatment has traditionally been a combination of medical management and intervention, including both carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TF-CAS). In recent years, transcarotid artery revascularization (TCAR) has been adopted as a promising treatment following FDA approval in 2015. In terms of stroke reduction, TCAR has been found to have equivalent outcomes with CEA with shorter operative times.

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Heart failure (HF) is a conundrum in that, current therapies only slow the progression of the disease. We posit, if the causal mechanism were targeted, progression of the disease could be stopped and potentially reversed. We hypothesize that insufficient myocardial blood flow (MBF) produces minute areas of ischemia, that lead to an accumulating injury culminating in HF.

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