肾素-血管紧张素-醛固酮系统激活及其他代谢变量与 HIV 患者动脉炎症的关系
Role of renin-angiotensin-aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV.
机构信息
Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
INOVA Heart and Vascular Institute, Falls Church, Virginia, USA.
出版信息
Clin Endocrinol (Oxf). 2022 Nov;97(5):581-587. doi: 10.1111/cen.14784. Epub 2022 Jun 6.
BACKGROUND
Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin-angiotensin-aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH.
DESIGN
Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS-activated and RAAS-suppressed state, respectively. We measured serum lipoprotein-associated phospholipase A2 (LpPLA2) concentrations following both conditions to assess the physiologic dynamics of aldosterone in relation to arterial inflammation.
RESULTS
LpPLA2 levels were significantly higher among PWH versus PWOH during both the RAAS-activated state[5.3(4.2, 6.1) versus 4.0(3.0, 4.8)nmol/L, median(interquartile range),p = .01]) and RAAS-suppressed state[4.4(3.9, 5.3) versus 3.8(3.4, 4.1)nmol/L,p = .01]. Among PWH, but not PWOH, LpPLA2 increased significantly with RAAS activation(p = .03). LpPLA2 levels measured during the RAAS-suppressed state among PWH remained relatively higher than LpPLA2 levels under both conditions among PWOH. Log LpPLA2 was related to log aldosterone during the RAAS-activated state(r = .39,p = .04) among all participants. Log LpPLA2 was correlated with visceral fat(r = .46,p = .04) and log systolic blood pressure(r = .57,p = .009) during a RAAS-activated state when an increase in aldosterone was stimulated in HIV.
CONCLUSION
LpPLA2 is increased during a RAAS-activated state among PWH, but not among PWOH. Further, LpPLA2 was increased in both RAAS-activated and suppressed states in PWH compared with PWOH. These data suggest a biological link between increased aldosterone and arterial inflammation in this population. Future studies should test RAAS blockade on arterial inflammation as a targeted treatment approach in HIV.
背景
即使控制了传统的危险因素，HIV 感染者（PWH）的动脉炎症仍高于非 HIV 感染者（PWOH）。我们试图了解在 PWH 中，肾素-血管紧张素-醛固酮系统（RAAS）的激活是否与动脉炎症有关，以及与 PWOH 相比情况如何。
设计
20 名 PWH 和 9 名 PWOH 遵循控制的、标准化的低钠和高钠饮食，以分别模拟 RAAS 激活和抑制状态。在两种情况下，我们都测量了血清脂蛋白相关磷脂酶 A2（LpPLA2）浓度，以评估醛固酮与动脉炎症之间的生理动态关系。
结果
在 RAAS 激活状态下，PWH 的 LpPLA2 水平明显高于 PWOH[5.3(4.2, 6.1)比 4.0(3.0, 4.8)nmol/L，中位数（四分位距），p=0.01]，在 RAAS 抑制状态下也高于 PWOH[4.4(3.9, 5.3)比 3.8(3.4, 4.1)nmol/L，p=0.01]。在 PWH 中，但在 PWOH 中没有，LpPLA2 随着 RAAS 的激活而显著增加（p=0.03）。在 PWH 中，RAAS 抑制状态下测量的 LpPLA2 水平仍然高于 PWOH 在两种情况下的 LpPLA2 水平。在所有参与者中，RAAS 激活状态下的 LpPLA2 对数与醛固酮对数呈正相关（r=0.39，p=0.04）。当 HIV 中醛固酮增加时，RAAS 激活状态下的 LpPLA2 与内脏脂肪（r=0.46，p=0.04）和收缩压（r=0.57，p=0.009）呈正相关。
结论
在 PWH 中，RAAS 激活状态下 LpPLA2 增加，但 PWOH 中则没有。此外，与 PWOH 相比，PWH 中 LpPLA2 在 RAAS 激活和抑制状态下均增加。这些数据表明，在该人群中，醛固酮增加与动脉炎症之间存在生物学联系。未来的研究应该测试 RAAS 阻断对 HIV 中动脉炎症的靶向治疗效果。
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