Disease relevance of SCARF1

• We suggest that atherogenesis in human arteries may be linked to macrophage-induced oxidative modification of LDL mediated by 15-lipoxygenase, leading to subsequent enhanced macrophage uptake, partly by way of the acetyl LDL receptor [1].

High impact information on SCARF1

• Moreover, these same lesions express abundant mRNA for the acetyl LDL receptor but no detectable mRNA for the LDL receptor [1].
• Previous studies have established that low density lipoprotein (LDL) incubated with endothelial cells (EC) undergoes extensive oxidative modification in structure and that the modified LDL is specifically recognized by the acetyl LDL receptor of the macrophage [2].
• The binding and uptake of oxidatively modified low density lipoprotein (OxLDL) by mouse peritoneal macrophages occurs, in part, via the well characterized acetyl LDL receptor [3].
• Macrophages specifically bind and internalize oxidatively modified low density lipoprotein (LDL) via the acetyl-LDL receptor and possibly one or more additional receptors jointly designated here as scavenger receptors [4].
• In the human monocytic cell line THP-1, the expression of both acetyl LDL receptor activity and a 220-kDa acetyl LDL binding protein were dramatically induced in parallel after differentiation to a macrophage-like state induced by phorbol ester [5].

Biological context of SCARF1

• The transcription start site of the SREC gene was mapped, and DNA sequence analysis revealed an Sp1 binding site in its proximal region [6].
• Analysis of full-length cDNA clones of SREC from a peripheral blood leukocyte cDNA library revealed that at least five alternatively spliced cDNAs were present, and two of them encoded soluble forms of SREC [6].
• The SREC gene spans 12 kilobase pairs and contains 11 exons [6].
• Excess amounts of acetyl-LDL or polyinosinic acid inhibited the uptake of these insoluble heparin proteoglycan-LDL complexes, indicating that their phagocytosis was mediated by scavenger receptors of the acetyl-LDL receptor type [7].

Anatomical context of SCARF1

• In the current study, we have isolated, by expression cloning, the cDNA encoding a novel type of scavenger receptor expressed by endothelial cells (SREC), which mediates the binding and degradation of Ac-LDL [8].
• Thus, cytokines have the potential to modulate the acetyl-LDL receptor pathway and to influence the rate of foam cell generation [9].
• Induction of acetyl-LDL receptor activity by phorbol ester in human monocyte cell line THP-1 [10].
• Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms [11].
• We prospectively reviewed 24 patients (35 feet) who had been treated by a Scarf osteotomy and Akin closing-wedge osteotomy for hallux valgus between June 2000 and June 2002 [12].

Associations of SCARF1 with chemical compounds

• There are a number of possible mechanisms by which macrophages might accumulate cholesterol, and one that has attracted much interest recently involves the uptake of oxidatively modified low density lipoprotein (LDL) via a specific cell surface receptor, termed the scavenger or acetyl-LDL receptor [13].
• These findings suggest that oxidation of LDL is accompanied by derivatization of lysine epsilon-amino groups by lipid products and that these adducts may be important in the interaction of oxidized LDL with the acetyl-LDL receptor [14].
• Acetyl-LDL receptor-mediated degradation was calcium independent, inhibited by chloroquine, and was sensitive to pronase and fucoidin treatments [15].

Physical interactions of SCARF1

• Whereas purified recombinant Sp1 alone produced similar protection in in vitro DNase I footprinting analysis, EZF-2 also bound to the 5'-flanking region SREC promoter [6].

Other interactions of SCARF1

• A novel transcription factor, endothelial zinc finger protein-2 (EZF-2), that binds to the 5'-flanking critical region of the SREC promoter activity was cloned from a HUVEC cDNA library employing a one-hybrid system [6].
• Taken together, these data indicate that human monocyte-macrophages exhibit a high affinity, saturable, specific, apoE- and lipoprotein lipase-independent binding site and membrane binding proteins for TGRLP that differ in expression, specificity, and molecular size from receptors of the LDL receptor gene family or the acetyl LDL receptor [16].
• These results show that the acetyl-LDL receptor recognizes an epitope on the apoprotein moiety, either newly generated or exposed as a result of oxidative modification, rather than some oxidized lipid moiety [17].
• The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF [18].

Analytical, diagnostic and therapeutic context of SCARF1

• According to the results, in patients with normal bone stock who are compliant, any of the four shoe types tested may be used after a Ludloff, Scarf, biplanar wedge (plantar screw fixation), or Mau osteotomy, but the wedge-based shoe should be used after a proximal crescentic or chevron osteotomy or for patients with severe osteopenic bone [19].
• Improvements in the technology have made endoscopic third ventriculostomy safer than earlier technics of open third ventriculostomy as described by Scarf (14) [20].

References