SARS-CoV-2如何导致心脏病和中风

概要

众所周知，COVID-19会增加心脏病发作和中风的风险。在严重的情况下，全身发生的强烈炎症可能会导致这种风险增加。纽约大学医学院的研究小组分析了2020年5月至2021年5月期间死于COVID-19的8名患者的冠状动脉组织样本，在《自然》杂志上2023年9月28日心血管研究版块发布了研究结果。

研究小组在所有患者的冠状动脉组织中发现了SARS-CoV-2病毒RNA，动脉壁中比周围脂肪组织有更多的病毒RNA，且许多受感染的细胞是巨噬细胞。值得一提的是，当巨噬细胞充满胆固醇时，它们被称为泡沫细胞。动脉内泡沫细胞的积聚形成斑块，这是动脉粥样硬化的标志。研究小组证实，SARS-CoV-2可以感染培养皿中的人类巨噬细胞和泡沫细胞。泡沫细胞比巨噬细胞更容易受到感染。这可以解释为什么患有动脉粥样硬化的人更容易感染COVID-19。

在这两种细胞类型中，感染取决于细胞表面的一种称为神经毡蛋白的蛋白质。关闭这些细胞中的神经毡蛋白基因可以减少感染。阻止病毒与神经毡蛋白结合也是如此。

感染会引发巨噬细胞和泡沫细胞中的多种炎症途径。这些细胞还释放出已知会导致心脏病和中风的分子。在通过手术从患者身上切除的动脉斑块中，研究人员发现了对SARS-CoV-2感染的炎症反应。 

研究结果表明，SARS-CoV-2可能通过感染动脉壁组织（包括相关巨噬细胞）来增加心脏病和中风的风险。这会引发动脉粥样硬化斑块的炎症，从而可能导致心脏病发作或中风。

How SARS-CoV-2 contributes to heart attacks and strokes

Foam cells, which accumulate within arteries to form plaques in atherosclerosis, proved particularly susceptible to infection with SARS-CoV-2. Kateryna Kon / Shutterstock

COVID-19 is known to increase the risk of heart attack and stroke. The intense inflammation that occurs throughout the body in severe cases likely contributes to this increased risk. But it’s not clear whether SARS-CoV-2, the virus that causes COVID-19, also affects blood vessels directly. 

To find out, an NIH-funded research team, led by Dr. Chiara Giannarelli at New York University School of Medicine, analyzed coronary artery tissue samples from eight people who died of COVID-19 between May 2020 and May 2021. Results appeared in Nature Cardiovascular Research on September 28, 2023.

The team found SARS-CoV-2 viral RNA in coronary artery tissue from all patients. They found more viral RNA in the arterial walls than in the surrounding fat tissue. Many of the infected cells were macrophages, a type of white blood cell that ingests pathogens. Samples with more macrophages had more viral RNA.

Macrophages also help remove cholesterol from blood vessels. When macrophages become laden with cholesterol, they are known as foam cells. Accumulation of foam cells within arteries forms plaques that are a hallmark of atherosclerosis. The team confirmed that SARS-CoV-2 could infect human macrophages and foam cells in a petri dish. The foam cells were much more susceptible to infection than the macrophages. This could explain why people with atherosclerosis are more vulnerable to COVID-19.

In both cell types, infection depended on a protein on the surface of the cells called neuropilin. Turning off the gene for neuropilin in these cells reduced infection. So did blocking the virus from binding to neuropilin.

Infection triggered several inflammatory pathways in macrophages and foam cells. The cells also released molecules that are known to contribute to heart attacks and strokes. In arterial plaques that had been surgically removed from patients, the researchers saw an inflammatory response to SARS-CoV-2 infection like that seen in the cultured cells. 

The findings suggest that SARS-CoV-2 may increase the risk of heart attacks and stroke by infecting artery wall tissue, including associated macrophages. This provokes inflammation in atherosclerotic plaques, which could lead to heart attack or stroke.

“These results shed light onto a possible connection between preexisting heart issues and Long COVID symptoms,” Giannarelli says. “It appears that the immune cells most involved in atherosclerosis may serve as a reservoir for the virus, giving it the opportunity to persist in the body over time.”

“Since the early days of the pandemic, we have known that people who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection,” says Dr. Michelle Olive of NIH’s National Heart, Lung, and Blood Institute. “We believe we have uncovered one of the reasons why.”

The authors plan to further investigate the potential link between infection of the arteries and Long COVID. They also aim to see if their results also hold true for newer SARS-CoV-2 variants.

—by Brian Doctrow, Ph.D.

Source：

National Institutes of Health

Published on 24 October, 2023

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