Figure 4.

Fold change in the expression of HS biosynthetic enzymes and core proteins in chronic inflammatory diseases. We analyzed microarray data on expression of HS core protein and biosynthetic enzymes in macrophages isolated from chronically inflamed tissues from more M1- (yellow) or M2-associated (green) diseases by FACS or laser-capture microdissection. Genes which were increased in disease compared with control are marked in red (p<0.05) or pink (p>0.05) and downregulated genes are marked in dark blue (p<0.05) or light blue (p>0.05). Kang,⁴⁷ Yarilina,⁴⁸ and You⁴⁹ compared freshly isolated CD14+ cells from human RA synovial fluid to CD14+ monocyte-derived macrophages (MDM) from healthy donors. Hägg⁵³ compared MDMs isolated from blood of patients with subclinical atherosclerosis and a family history of CVD after exposure to oxidized LDL (oxLDL) to mimic the atherosclerotic environment with those from healthy donors. Woodruff,⁵² Shaykhiev,⁵⁰ and Kazeros⁵¹ compared macrophages isolated from broncheoalveolar lavage from smokers, patients with asthma or COPD to those of healthy donors. Goo⁵⁴ compared microdissected macrophages from the aorta of ApoE^–/^– mice on a high fat western-type diet (WTD) for 14 weeks to a normal diet. Feig⁵⁵ compared microdissected macrophages in a progression (Pr) or regression (Re) model of atherosclerosis, which promoted M1 or M2 polarization, respectively. Berisha⁵⁶ compared bone marrow-derived macrophages (BMDM) from male (M) or female (F) atherosclerosis-resistant ApoE^–/– AKR mice to BMDM from atherosclerosis-prone ApoE^–/– DBA/2 mice after loading with acetylated LDL (acLDL). Aurora⁵⁷ compared CD11b⁺Ly6G^– macrophages from the heart of mice 3 days after experimental myocardial infarction at postnatal day 14 (P14; nonregenerating) to P1 (regenerating). Xu⁵⁸ compared CD11c⁺ and CD11c^– (generally considered to represent M1 and M2 macrophages) CD11b⁺F4/80⁺ macrophages from the perigonodal cells of leptin-deficient obese mice to wild-type mice. Although HS-associated genes were differentially expressed upon obesity in CD11c⁺ macrophages, no differences were observed in CD11c^– macrophages. Prieur⁵⁹ compared CD11b⁺ macrophages from gonadal white adipose tissue of leptin-deficient obese mice after 5 (5W) or 16 weeks (16W) of WTD to wild-type mice. They demonstrated that macrophages have a more M2-like phenotype after 5 weeks and more M1-like after 16 weeks of diet. Abbreviations: HS, heparan sulfate; RA, rheumatoid arthritis; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; ApoE, apolipoprotein E.