Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circ J. 2010 Feb;74(2):213-20. doi: 10.1253/circj.cj-09-0706. Epub 2010 Jan 9.
Inflammation drives the formation, progression, and rupture of atherosclerotic plaques. Experimental studies have demonstrated that an inflammatory subset of monocytes/macrophages preferentially accumulate in atherosclerotic plaque and produce proinflammatory cytokines. T lymphocytes can contribute to inflammatory processes that promote thrombosis by stimulating production of collagen-degrading proteinases and the potent procoagulant tissue factor. Recent data link obesity, inflammation, and modifiers of atherosclerotic events, a nexus of growing clinical concern given the worldwide increase in the prevalence of obesity. Modulators of inflammation derived from visceral adipose tissue evoke production of acute phase reactants in the liver, implicated in thrombogenesis and clot stability. Additionally, C-reactive protein levels rise with increasing levels of visceral adipose tissue. Adipose tissue in obese mice contains increased numbers of macrophages and T lymphocytes, increased T lymphocyte activation, and increased interferon-gamma (IFN-gamma) expression. IFN-gamma deficiency in mice reduces production of inflammatory cytokines and inflammatory cell accumulation in adipose tissue. Another series of in vitro and in vivo mouse experiments affirmed that adiponectin, an adipocytokine, the plasma levels of which drop with obesity, acts as an endogenous antiinflammatory modulator of both innate and adaptive immunity in atherogenesis. Thus, accumulating experimental evidence supports a key role for inflammation as a link between risk factors for atherosclerosis and the biology that underlies the complications of this disease. The recent JUPITER trial supports the clinical utility of an assessment of inflammatory status in guiding intervention to limit cardiovascular events. Inflammation is thus moving from a theoretical concept to a tool that provides practical clinical utility in risk assessment and targeting of therapy.
炎症导致动脉粥样硬化斑块的形成、进展和破裂。实验研究表明，单核细胞/巨噬细胞的一个炎症亚群优先在动脉粥样硬化斑块中积聚，并产生促炎细胞因子。T 淋巴细胞可通过刺激胶原降解蛋白酶和强效促凝组织因子的产生，促进促进血栓形成的炎症过程。最近的数据将肥胖、炎症和动脉粥样硬化事件的调节剂联系起来，鉴于肥胖在全球的普遍增加，这是一个日益引起临床关注的焦点。源自内脏脂肪组织的炎症调节剂会引起肝脏产生急性期反应物，这些反应物与血栓形成和血栓稳定性有关。此外，C 反应蛋白水平随内脏脂肪组织水平的升高而升高。肥胖小鼠的脂肪组织中含有更多的巨噬细胞和 T 淋巴细胞，T 淋巴细胞的激活增加，干扰素-γ（IFN-γ）表达增加。IFN-γ 缺乏会减少炎症细胞因子的产生和脂肪组织中炎症细胞的积聚。另一系列体外和体内小鼠实验证实，脂联素是一种脂肪细胞因子，其在肥胖时血浆水平下降，作为动脉粥样硬化发生过程中固有和适应性免疫的内源性抗炎调节剂。因此，越来越多的实验证据支持炎症作为动脉粥样硬化危险因素与该疾病并发症基础生物学之间的联系的关键作用。最近的 JUPITER 试验支持通过评估炎症状态来指导干预以限制心血管事件的临床实用性。因此，炎症正在从一个理论概念转变为一种提供实用临床实用性的风险评估和靶向治疗的工具。
