Dichotomous effects of isomeric secondary amines containing an aromatic nitrile and nitro group on human aortic smooth muscle cells via inhibition of cystathionine-γ-lyase

Abstract

Excessive proliferation of vascular smooth muscle cells (SMC) is an important contributor to the progression of atherosclerosis. Inhibition of proliferation can be achieved by endogenously produced and exogenously supplied nitrogen monoxide, commonly known as nitric oxide (NO). We report herein the dichotomous effects of two isomeric families of secondary amines, precursors to the N-nitrosated NO-donors, on HASMC proliferation. The syntheses of these two families were carried out using two equivalents of homologous, aliphatic monoamines and 2,6-difluoro-3-nitrobenzonitrile (2,6-DFNBN, O family) or 2,4-difluoro-5-nitrobenzonitrile (2,4-DFNBN, P family). The secondary amines belonging to the P family inhibited HASMC proliferation at all concentrations, whereas the O family induced HASMC proliferation at low concentrations, and exhibited inhibitory properties at high concentrations. A probable explanation of these behaviors is proposed herein. L-homocysteine (HCY) is known to induce HASMC proliferation at low concentrations (<1mM) and inhibit HASMC proliferation at higher concentrations (>2.5 mM). Our findings suggest that these two families of amines inhibit cystathionine-γ-lyase (CSE) to varying extents, which directly results in altered levels of intracellular HCY and consequent changes in HASMC proliferation.

Comparative analyses of copy number variations between Bos taurus and Bos indicus

“…We did blast the ENSBTAG00000004415 sequence against the cattle genome (ARS-UCD1.2) and found that the second exon of the ENSBTAG00000004415 was actually a retropseudogene of CTH in Bos taurus . Previous studies showed that both the CTH and the CTNNA1 functioned in the muscle cell differentiation [ 39 , 42 ]. We speculated that this CNV segment (chr7:50070412–50,072,341) may be related to the muscle development difference between Bos taurus and Bos indicus , through regulating ENSBTAG00000004415 and CTNNA1.…”

“…Previous studies showed that both the Fig. 3 PCA analysis of the ten cattle breeds based on the CNV CTH and the CTNNA1 functioned in the muscle cell differentiation [39,42]. We speculated that this CNV segment (chr7:50070412-50,072,341) may be related to the muscle development difference between Bos taurus and Bos indicus, through regulating ENSBTAG00000004415 and CTNNA1.…”

Classical and Deep Learning Paradigms for Detection and Validation of Key Genes of Risky Outcomes of HCV

“…Cystathionine gamma-lyase, CTH, has been detected as downregulated. CTH encodes an enzyme in the cellular processes of liver and kidney and it is a prognostic biomarker for bladder cancer [41]. CHAC1 has only been detected in the first and second periods of post-infection.…”