Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
J Eur Acad Dermatol Venereol. 2013 Jan;27(1):37-42. doi: 10.1111/j.1468-3083.2011.04354.x. Epub 2011 Nov 24.
Apelin is a bioactive peptide exerting its pro-angiogenic and pro-fibrotic effects in a context-dependent manner through the activation of its receptor APJ, which is ubiquitously expressed on the surface of various cell types. The activation of apelin/APJ signalling appears to be involved in the pathological process of fibrotic disorders, including liver cirrhosis.
As an initial step to clarify the role of apelin/APJ signalling in the pathogenesis of systemic sclerosis (SSc), we investigated serum apelin levels and their clinical association in patients with SSc.
Serum apelin levels were determined by a specific enzyme-linked immunosorbent assay in 56 SSc patients and 18 healthy controls.
Serum apelin levels were comparable among three groups, including diffuse cutaneous SSc, limited cutaneous SSc and control subjects (1.77 ± 1.48, 1.63 ± 1.51 and 1.61 ± 0.44 ng/mL, respectively). When we classified SSc patients into three groups according to disease duration, serum apelin levels were elevated in early SSc (<3 years) compared with mid-stage SSc (3-10 years) (1.74 ± 1.26 vs. 1.02 ± 0.52 ng/mL, P < 0.05). Importantly, in late stage SSc (>10 years), the prevalence of severe vascular involvements, including intractable skin ulcers, scleroderma renal crisis and pulmonary arterial hypertension, was significantly higher in patients with elevated serum apelin levels than in those without (100% vs. 20%, P < 0.05).
Apelin may be associated with altered and activated angiogenesis prior to fibrotic responses in early SSc and with the development of proliferative vasculopathy in late stage SSc.
Apelin 是一种生物活性肽,通过其受体 APJ 的激活,以依赖于上下文的方式发挥其促血管生成和促纤维化作用,APJ 广泛表达于各种细胞类型的表面。Apelin/APJ 信号的激活似乎与纤维化疾病的病理过程有关,包括肝硬化。
为了阐明 Apelin/APJ 信号在系统性硬化症(SSc)发病机制中的作用,我们研究了 SSc 患者血清 Apelin 水平及其与临床的相关性。
采用特异性酶联免疫吸附试验测定 56 例 SSc 患者和 18 例健康对照者血清 Apelin 水平。
三组患者(弥漫性皮肤 SSc、局限性皮肤 SSc 和对照组)血清 Apelin 水平无差异(分别为 1.77±1.48、1.63±1.51 和 1.61±0.44ng/ml)。根据疾病持续时间将 SSc 患者分为三组,早期 SSc(<3 年)患者血清 Apelin 水平高于中晚期 SSc(3-10 年)(1.74±1.26 vs. 1.02±0.52ng/ml,P<0.05)。重要的是,在晚期 SSc(>10 年)中,血清 Apelin 水平升高的患者比无升高的患者更容易出现严重血管并发症,包括难治性皮肤溃疡、硬皮病肾危象和肺动脉高压(100% vs. 20%,P<0.05)。
Apelin 可能与早期 SSc 纤维化反应前的血管生成改变和激活有关,与晚期 SSc 增殖性血管病变的发生有关。