血漿血管張力素轉換酶2在原發性高醛固酮症中的角色

林彥均¹、吳允升^2,5、彭康詠²、詹傑凱³、闕士傑^4,5

¹國立台灣大學醫學院附設醫院雲林分院 泌尿部; ²國立台灣大學醫學院附設醫院 內科部; ³國立台灣大學醫學院附設醫院新竹分院 內科部; ⁴國立台灣大學醫學院附設醫院 泌尿部; ⁵台灣原發性高醛固酮症研究團隊

The Role of Plasma Angiotensin-Converting Enzyme 2 in Primary Aldosteronism

Yen-Chun Lin¹, Vin-Cent Wu^2,5, Kang-Yung Peng², Chieh-Kai Chan³, Jeff S Chueh^4,5

¹ National Taiwan University Hospital Yunlin branch, Urology Department, Yunlin County, Taiwan

² Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

³ Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu branch, Hsin-Chu County, Taiwan

⁴ Department of Urology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

⁵ TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taipei, Taiwan

Purpose

  Plasma angiotensin-converting enzyme 2 ( ([pACE2], via proteolytic shedding of membrane-bound ACE2)) is a key regulator of the renin–angiotensin system in cardiovascular disease. The purpose of this study was to discuss the role of pACE2 in primary aldosteronism (PA) and relationships in treatments.

Materials and Methods

  We examined [pACE2] in 168 incident primary aldosteronism (PA), 40 essential hypertension (EH) patients and 24 normotensive controls through an observational cohort. Ipsilateral adrenalectomy or mineralocorticoid receptor antagonist (MRA) therapy were performed in patients with Unilateral PA (uPA). We assessed the expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) by peripheral blood mononuclear cells (PBMCs).

Results

  It revealed similar elevation [pACE2] (47.04±22.06 vs. 46.73±21.06 ng/ml, p= 0.937) in patients of incident PA and EH. Relatively higher serum potassium levels (β, 2.29, p= 0.024) and younger age (β, 2.15, p= 0.033) seemed to show positive correlation with higher [pACE2] in PA patients . PASO clinical complete hypertension-remission was achieved in 36 (50%) of the 72 surgically-treated uPA patients. We also noticed that [pACE2] decreasing in surgically-treated patients who had (p< 0.001) or had no (p= 0.006) hypertension-remission during follow-up, but there was no significance in the [pACE2] attenuation in both uPA (p= 0.085) and biPA (p= 0.409) cases administered with MRA. [pACE2] (> 23ng/ml) elevation after targeted treatments in PA patients related to all-cause mortality and cardiovascular events among PA patients (HR, 8.8, p=0.04) with a mean follow- up of 2.29 years. uPA (p= 0.018) and EH (p= 0.038) patients had higher TMPRSS2 mRNA expression than in normotensive controls; furthermore, decreased TMPRSS2 mRNA expression was also discovered in cases after adrenalectomy (p< 0.001).

Conclusions

  Elevated [pACE2] and higher expression of TMPRSS2 mRNA was found in PA and EH patients compared to those of normotensive population. [pACE2] (> 23ng/ml) elevation after targeted treatments was associated with cardiovascular events and risk of mortality. Irrespective of  their hypertension-remission status, uPA patients who underwent adrenalectomy showed decreased [pACE2] and attenuated expression of TMPRSS2. However, PA patients with MRA administration could not decrease their [pACE2].