Zhang Xin, Krier James D, Amador Carrascal Carolina, Greenleaf James F, Ebrahimi Behzad, Hedayat Ahmad F, Textor Stephen C, Lerman Amir, Lerman Lilach O
Division of Nephrology and Hypertension and.
Departments of Physiology and Biomedical Engineering and.
J Am Soc Nephrol. 2016 Dec;27(12):3715-3724. doi: 10.1681/ASN.2015060704. Epub 2016 Jun 13.
Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low-energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low-energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low-energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo A 3-week low-energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low-energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low-energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.
肾动脉狭窄远端的微血管稀疏与肾功能障碍及不良预后相关。低能量冲击波疗法可刺激血管生成,但对肾脏微血管系统的影响尚不清楚。我们推测低能量冲击波疗法可恢复肾血管疾病中的微循环并减轻肾功能障碍。对正常猪和接受3周肾动脉狭窄的猪进行六次低能量冲击波治疗(连续3周,每两周一次)或不进行治疗。在治疗完成4周后,我们在体内评估血压、尿蛋白、狭窄肾血流量、肾小球滤过率、微血管结构和氧合,然后在体外评估血管生成因子和机械转导蛋白(粘着斑激酶和β1整合素)的表达。为期3周的低能量冲击波疗法可减轻肾血管性高血压,使狭窄肾脏的微血管密度和氧合正常化,稳定功能,并减轻肾动脉狭窄猪的纤维化。这些作用与肾脏血管生成因子和机械转导蛋白表达升高有关,尤其是在近端肾小管细胞中。在肾动脉狭窄延长(6周)的其他猪中,冲击波疗法也降低了血压,并改善了狭窄肾脏的肾小球滤过率、微血管密度和氧合。这种冲击波疗法在正常猪中未引起可检测到的肾损伤。总之,低能量冲击波疗法可改善狭窄肾脏的功能,可能部分是通过近端肾小管细胞中血管生成因子的机械转导介导表达实现的,并且它可能改善肾血管性高血压。低能量冲击波疗法可能成为肾血管疾病管理中的一种新型非侵入性干预措施。