Shainkin-Kestenbaum R, Zimlichman S, Lis M, Lidor C, Pomerantz M, Knyszynski A, Preciado-Patt L, Fridkin M
Biochemical Laboratory, Meir Hospital, Sapir Medical Center, Kfar-Saba, Israel.
Biomed Pept Proteins Nucleic Acids. 1996;2(3):79-84.
The possible contribution of apo-HDL serum amyloid A (SAA) to the protective effect of HDL against atherosclerosis was studied by evaluating its effect on bovine aortic endothelial cell (BAEC) proliferation. Our results suggest that human SAA, both purified and recombinant, in concentrations relevant to mild acute phase events, significantly inhibit endothelial cell proliferation in a dose-dependent manner (e.g., 50 micrograms/ml causes approximately 88% inhibition; p < 0.001). This inhibition was attenuated by addition of fibroblast growth factor (FGF), which antagonized the SAA-mediated effect. As levels of TNF may be highly elevated during the acute phase response, its effect on BAEC proliferation was evaluated and found, at concentrations of > 1 pg/ml, to be substantially inhibitory Co-incubation of cells with both SAA and TNF was inhibitory, albeit neither additive nor synergistic. FGF antagonized the effect of both proteins. Amyloidic deposit (AA, i.e. SAA 1-76), derived from pathological proteolysis of SAA, practically retains the inhibitory activity (e.g. 50 micrograms/ml causes approximately 66% inhibition; p < 0.001) but apparently lacks the regulatory site towards FGF. In contrast to the above inhibitory effect, synthetic SAA-related peptide corresponding to the sequence 29-33 of SAA enhances BAEC proliferation (50 micrograms/ml causes approximately 64% increase; p < 0.001). The present data, coupled with our previous observations in which SAA was found to induce endothelial PGI2 formation and to inhibit overproduction of PGI2 by TNF and LPS as well as platelet aggregation, may suggest that SAA contributes to the protective effect of HDL against atherosclerosis. This, by means of its modulatory effect on endothelial cell and platelet activation, primarily in the presence of other regulatory proteins. SAA-derived peptides may, potentially, be used as therapeutic agents in the treatment of atherosclerosis and cardiovascular diseases.
通过评估载脂蛋白 - 高密度脂蛋白血清淀粉样蛋白A（SAA）对牛主动脉内皮细胞（BAEC）增殖的影响，研究了其在高密度脂蛋白对动脉粥样硬化保护作用中的潜在贡献。我们的结果表明，纯化的和重组的人SAA在与轻度急性期事件相关的浓度下，以剂量依赖的方式显著抑制内皮细胞增殖（例如，50微克/毫升导致约88％的抑制；p <0.001）。添加成纤维细胞生长因子（FGF）可减弱这种抑制作用，FGF可拮抗SAA介导的效应。由于急性期反应期间TNF水平可能会大幅升高，因此评估了其对BAEC增殖的影响，发现在浓度> 1 pg/ml时具有显著抑制作用。细胞与SAA和TNF共同孵育具有抑制作用，尽管既无相加作用也无协同作用。FGF拮抗这两种蛋白质的作用。源自SAA病理蛋白水解的淀粉样沉积物（AA，即SAA 1 - 76）实际上保留了抑制活性（例如，50微克/毫升导致约66％的抑制；p <0.001），但显然缺乏对FGF的调节位点。与上述抑制作用相反，对应于SAA序列29 - 33的合成SAA相关肽可增强BAEC增殖（50微克/毫升导致约64％的增加；p <0.001）。目前的数据，结合我们之前的观察结果，即发现SAA可诱导内皮细胞形成前列环素（PGI2）并抑制TNF、LPS以及血小板聚集引起的PGI2过度产生，可能表明SAA有助于高密度脂蛋白对动脉粥样硬化的保护作用。这是通过其对内皮细胞和血小板活化的调节作用实现的，主要是在存在其他调节蛋白的情况下。源自SAA的肽可能潜在地用作治疗动脉粥样硬化和心血管疾病的治疗剂。
