Facultad de Medicina, Departamentos de Fisiologia, Universidad Autonoma de Madrid, Madrid Spain.
Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H1153-65. doi: 10.1152/ajpheart.00886.2010. Epub 2011 Jun 3.
Liver growth factor (LGF) is an endogenous albumin-bilirubin complex with antihypertensive effects in spontaneously hypertensive rats (SHR). We assessed the actions of LGF treatment on SHR mesenteric resistance and intramyocardial arteries (MRA and IMA, respectively), heart, and vascular smooth muscle cells (VSMC). SHR and Wistar-Kyoto (WKY) rats treated with vehicle or LGF (4.5 μg LGF/rat, 4 ip injections over 12 days) were used. Intra-arterial blood pressure was measured in anesthetized rats. The heart was weighted and paraffin-embedded. Proliferation, ploidy, and fibronectin deposition were studied in carotid artery-derived VSMC by immunocytochemistry. In MRA, we assessed: 1) geometry and mechanics by pressure myography; 2) function by wire myography; 3) collagen by sirius red staining and polarized light microscopy, and 4) elastin, cell density, nitric oxide (NO), and superoxide anion by confocal microscopy. Heart sections were used to assess cell density and collagen content in IMA. Left ventricular hypertrophy (LVH) regression was assessed by echocardiography. LGF reduced blood pressure only in SHR. LGF in vitro or as treatment normalized the alterations in proliferation and fibronectin in SHR-derived VSMC with no effect on WKY cells. In MRA, LGF treatment normalized collagen, elastin, and VSMC content and passive mechanical properties. In addition, it improved NO availability through reduction of superoxide anion. In IMA, LGF treatment normalized perivascular collagen and VSMC density, improving the wall-to-lumen ratio. Paired experiments demonstrated a partial regression of SHR LVH by LGF treatment. The effective cardiovascular antifibrotic and regenerative actions of LGF support its potential in the treatment of hypertension and its complications.
肝生长因子 (LGF) 是一种内源性白蛋白-胆红素复合物，具有降血压作用，可用于自发性高血压大鼠 (SHR)。我们评估了 LGF 治疗对 SHR 肠系膜阻力和心肌内动脉（分别为 MRA 和 IMA）、心脏和血管平滑肌细胞（VSMC）的作用。使用给予载体或 LGF（4.5 μg LGF/大鼠，4 次腹腔内注射，共 12 天）处理的 SHR 和 Wistar-Kyoto（WKY）大鼠。在麻醉大鼠中测量动脉内血压。称重并将心脏包埋在石蜡中。通过免疫细胞化学研究颈动脉衍生的 VSMC 的增殖、倍性和纤维连接蛋白沉积。在 MRA 中，我们评估了：1）压力肌描记术评估几何形状和力学；2）通过线肌描记术评估功能；3）通过天狼星红染色和偏光显微镜评估胶原；4）通过共聚焦显微镜评估弹性蛋白、细胞密度、一氧化氮（NO）和超氧阴离子。心脏切片用于评估 IMA 中的细胞密度和胶原含量。通过超声心动图评估左心室肥厚 (LVH) 的消退。LGF 仅降低 SHR 的血压。LGF 体外或作为治疗可使 SHR 衍生的 VSMC 中的增殖和纤维连接蛋白改变正常化，而对 WKY 细胞无影响。在 MRA 中，LGF 治疗使胶原、弹性蛋白和 VSMC 含量以及被动机械特性正常化。此外，它通过减少超氧阴离子来提高 NO 的可用性。在 IMA 中，LGF 治疗使血管周围胶原和 VSMC 密度正常化，改善了壁腔比。配对实验表明，LGF 治疗可使 SHR 的 LVH 部分消退。LGF 的有效心血管抗纤维化和再生作用支持其在高血压及其并发症治疗中的潜力。
