Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low density lipoproteins have been implicated in the pathogenesis of atherosclerosis. A study has therefore been made of their proteolytic degradation by homogenates of cultured smooth muscle cells from the pig aorta. The pH optimum of proteolysis of 125I-labelled low density lipoproteins was 4.25, thus suggesting the involvement of lysosomal cathepsins. Proteolysis at acid pH started to become saturated at low density lipoprotein concentrations of approx. 20 microgram of protein/ml, but did not obey Michaelis-Menten kinetics. After a lag period of approx. 10 min, proteolytic degradation was linear with time up to at least 4 h incubation, but showed a sigmoidal relationship with homogenate concentration. When cathepsin D was inhibited by pepstatin, the proteolysis of 125I-labeled low density lipoproteins was inhibited by more than 90%, whereas when cathepsin B was inhibited by leupeptin, the rate of proteolysis decreased by approx. 50%. Antipain, which inhibits both cathepsins A and B, did not inhibit proteolysis any more than leupeptin, thus suggesting a minor role, if any, for cathepsin A. a combination of pepstatin and either leupeptin or antipain inhibited proteolysis completely. Cathepsins B and D acted synergistically in the degradation of 125I-labelled low density lipoproteins.
 ...
PMID:Proteolytic degradation of low density lipoproteins by arterial smooth muscle cells: the role of individual cathepsins. 701 93

Cardiovascular disease (CVD) is responsible for the majority of deaths in the developed world. Particularly, in patients with chronic kidney disease (CKD), the imbalance of calcium and phosphate may lead to the acceleration of both vascular and valve inflammation and calcification. One in two patients with CKD are reported as dying from cardiovascular causes due to the resulting acceleration in the development of atherosclerosis plaques. In addition, CKD patients on hemodialysis are prone to aortic valve calcification and often need valve replacement before kidney transplantation. The lysosomal proteases, cathepsins, are composed of 11 cysteine members (cathepsin B, C, F, H, K, L, O, S, V, W, and Z), as well as serine proteases cathepsin A and G, which cleave peptide bonds with serine as the amino acid, and aspartyl proteases D and E, which use an activated water molecule bound to aspartate to break peptide substrate. Cysteine proteases, also known as thiol proteases, degrade protein via the deprotonation of a thiol and have been found to play a significant role in autoimmune disease, atherosclerosis, aortic valve calcification, cardiac repair, and cardiomyopathy, operating within extracellular spaces. This review sought to evaluate recent findings in this field, highlighting how among cathepsins, the inhibition of cathepsin S in particular, could play a significant role in diminishing the effects of CVD, especially for patients with CKD.
 ...
PMID:Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in Chronic Kidney Disease. 2937 89