Purpose

Remodeling of sympathetic nerves and ACE2 has been implicated in cardiac pathology, and ACE2 also serves as a receptor for SARS-CoV-2. However, there is limited histological knowledge about the transmural distribution of sympathetic nerves and the cellular localization and distribution of ACE2 in human left ventricles from normal or diseased hearts. Goals of this study were to establish the normal pattern for these parameters and determine changes that occurred in decedents with cardiovascular disease alone compared to those with cardiac pathology and severe COVID-19.

Methods

We performed immunohistochemical analysis on sections of left ventricular wall from twenty autopsied human hearts consisting of a control group, a cardiovascular disease group, and COVID-19 ARDS, and COVID-19 non-ARDS groups.

Results

Using tyrosine hydroxylase as a noradrenergic marker, we found substantial sympathetic nerve loss in cardiovascular disease samples compared to controls. Additionally, we found heterogeneous nerve loss in both COVID-19 groups. Using an ACE2 antibody, we observed robust transmural staining localized to pericytes in the control group. The cardiovascular disease hearts displayed regional loss of ACE2 in pericytes and regional increases in staining of cardiomyocytes for ACE2. Similar changes were observed in both COVID-19 groups.

Conclusions

Heterogeneity of sympathetic innervation, which occurs in cardiac disease and is not increased by severe COVID-19, could contribute to arrhythmogenesis. The dominant localization of ACE2 to pericytes suggests that these cells would be the primary target for potential cardiac infection by SARS-CoV-2. Regional changes in ACE2 staining by myocytes and pericytes could have complex effects on cardiac pathophysiology.

中文翻译：

---

心脏病患者会发生交感神经重塑和血管紧张素转换酶 2 定位改变，但重症 COVID-19 不会加剧这种情况

 目的

交感神经和 ACE2 的重塑与心脏病理学有关，ACE2 还充当 SARS-CoV-2 的受体。然而，关于交感神经的透壁分布以及 ACE2 在正常或患病心脏的人左心室中的细胞定位和分布的组织学知识有限。本研究的目标是建立这些参数的正常模式，并确定仅患有心血管疾病的死者与患有心脏病和严重 COVID-19 的死者相比发生的变化。

 方法

我们对 20 例尸检人心脏的左心室壁切片进行了免疫组织化学分析，其中包括对照组、心血管疾病组、COVID-19 ARDS 组和 COVID-19 非 ARDS 组。

 结果

使用酪氨酸羟化酶作为去甲肾上腺素能标记物，我们发现与对照组相比，心血管疾病样本中交感神经大量丧失。此外，我们发现两个 COVID-19 组中均存在异质性神经损失。使用 ACE2 抗体，我们观察到对照组周细胞的强透壁染色。心血管疾病心脏表现出周细胞中 ACE2 的区域性缺失以及心肌细胞 ACE2 染色的区域性增加。在两个 COVID-19 组中都观察到了类似的变化。

 结论

交感神经支配的异质性发生在心脏病中，并且不会因严重的 COVID-19 而增加，可能会导致心律失常。 ACE2 主要定位于周细胞，表明这些细胞可能是SARS-CoV-2 潜在心脏感染的主要目标。心肌细胞和周细胞 ACE2 染色的区域变化可能对心脏病理生理学产生复杂的影响。