Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction in pulmonary artery hypertension: till the dawn, waiting.

Neuro-hormonal activation may lead to or be associated with pulmonary arterial hypertension (PAH) and right ventricular dysfunction. Notwithstanding whether it is the cause or the consequence of PAH-related right ventricle (RV) dysfunction neurohormonal activation contributes to significant morbidity and mortality in patients with PAH and the progression of RV dysfunction. Experimental data regarding the use of beta adrenergic blockade and renin-angiotensin aldosterone system modulation are encouraging.

Inclusion bodies enriched for p62 and polyubiquitinated proteins in macrophages protect against atherosclerosis.

Autophagy is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. Atherosclerotic plaque formation is enhanced in mice with macrophages deficient for the critical autophagy protein ATG5. We showed that exposure of macrophages to lipids that promote atherosclerosis increased the abundance of the autophagy chaperone p62 and that p62 colocalized with polyubiquitinated proteins in cytoplasmic inclusions, which are characterized by insoluble protein aggregates.

Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid-induced lysosomal dysfunction and downstream sequelae.

Objective: Recent reports of a proatherogenic phenotype in mice with macrophage-specific autophagy deficiency have renewed interest in the role of the autophagy-lysosomal system in atherosclerosis. Lysosomes have the unique ability to process both exogenous material, including lipids and autophagy-derived cargo such as dysfunctional proteins/organelles. We aimed to understand the effects of an atherogenic lipid environment on macrophage lysosomes and to evaluate novel ways to modulate this system.

Autophagy links inflammasomes to atherosclerotic progression.

We investigated the role of autophagy in atherosclerosis. During plaque formation in mice, autophagic markers colocalized predominantly with macrophages (mφ). Atherosclerotic aortas had elevated levels of p62, suggesting that dysfunctional autophagy is characteristic of plaques.

Dendronized supramolecular nanocapsules: pH independent, water-soluble, deep-cavity cavitands assemble via the hydrophobic effect.

At neutral pH, dendronized deep-cavity cavitands were shown to form supramolecular nanocapsules via assembly around a range of guest molecules.