2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS).

Biosensors, Aarhus University Hospital, and participating sites.

No abstract

Objective-Human atherosclerotic lesions have been shown to contain lipid droplets and vesicles resembling those of in vitro enzymatically modified LDL. However, little is known about the hydrolytic enzymes in the arterial intima that induce fusion of LDL particles and so produce lipid droplets or that induce foam cell formation. Methods and Results-Human coronary atherosclerotic lesions obtained at surgery and at autopsy were stained for lysosomal acid lipase and cathepsin D. The extracellular areas of macrophage-rich intimal regions of the atherosclerotic lesions stained positively for both cathepsin D and lysosomal acid lipase, whereas normal arteries were negative. When monocyte-derived macrophages were incubated with opsonized zymosan to stimulate the release of lysosomal enzymes from the cells and LDL was incubated with the macrophage-conditioned media, the apolipoprotein B-100, cholesteryl esters, and triacylglycerols of LDL were hydrolyzed. These hydrolytic modifications rendered the LDL particles unstable and induced their fusion. Cultured macrophages and smooth muscle cells took up the hydrolase-modified LDL particles avidly and were transformed into foam cells. Key Words: macrophage Ⅲ lysosomal enzymes Ⅲ LDL Ⅲ atherosclerosis A therogenesis is characterized by accumulation of LDLderived lipids in the extracellular matrix of the arterial intima, recruitment of monocyte-derived macrophages, and their transformation into lipid-laden foam cells. 1 The lipid accumulates extracellularly in atherosclerotic lesions in the form of small lipid droplets and vesicles. 2 Modification of LDL in vitro by proteolysis, lipolysis, and oxidation has been shown to produce particles resembling those observed in the arterial intima. [3][4][5][6][7][8][9][10] Lipid particles enriched in unesterified cholesterol have been isolated from the human arterial intima, 11 and evidence for the presence of the particles resembling in vitro enzymatically modified LDL 3 has been provided by the immunohistochemistry. 12 However, the enzymes responsible for such LDL modification in the arterial intima have remained uncharacterized. Conclusions-Our See page 1312Two enzymes that participate in the hydrolysis of endocytosed LDL in the lysosomal compartment of cells are cathepsin D and lysosomal acid lipase (LAL). The former initiates the lysosomal degradation of apolipoprotein B-100 (apoB-100) 13 and is found in atherosclerotic intima. 14,15 The latter is normally responsible for lysosomal hydrolysis of cholesteryl esters and triacylglycerols of the endocytosed LDL particles. 16 Extracellular discharge of lysosomal enzymes is a common physiological response to a variety of inflammatory stimuli. 17,18 Under pathologic conditions, cathepsin D has been found extracellularly in many tissues, eg, in the invading edge of the rheumatoid synovium, 19 MethodsAn online Methods section is available at http://atvb.ahajournals.org. ResultsThe presence of the lysosomal enzymes cathepsin D and LAL was studied by immunohistochemistry in normal and in ather...