Hypertension is a major cause of cardiovascular diseases such as myocardial infarction and stroke. Cardiovascular fibrosis occurs with hypertension and contributes to vascular resistance, aortic stiffness, and cardiac hypertrophy. However, the molecular mechanisms leading to the fibroblast activation in hypertension remain largely unknown. There are two types of fibrosis: replacement fibrosis and reactive fibrosis. Replacement fibrosis occurs in response to the loss of viable tissue to form a scar. Reactive fibrosis occurs in response to increase in mechanical and neurohormonal stress. Although both types of fibrosis are considered as adaptive processes, they become mal-adaptive when the tissue loss is too large, or the stress persists. Myofibroblasts represent a subpopulation of activated fibroblasts that have gained contractile function to promote wound healing. Therefore, myofibroblasts are a critical cell type that promotes replacement fibrosis. Although myofibroblasts were recognized as the fibroblasts participating in reactive fibrosis, recent experimental evidence indicated there are distinct fibroblast populations in cardiovascular reactive fibrosis. Accordingly, we will discuss the updated definition of fibroblast subpopulations, the regulatory mechanisms, and their potential roles in cardiovascular pathophysiology utilizing new knowledge from various lineage tracing and single-cell RNA sequencing studies. Among the fibroblast subpopulations, we will highlight the novel roles of matrifibrocytes and immune fibrocytes in cardiovascular fibrosis including experimental models of hypertension, pressure overload, myocardial infarction, atherosclerosis, aortic aneurysm, and nephrosclerosis. Exploration into the molecular mechanisms involved in the differentiation and activation of those fibroblast subpopulations may lead to novel treatments for end-organ damage associated with hypertension and other cardiovascular diseases.

中文翻译：

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高血压中的心脏和血管周围肌成纤维细胞、基质纤维细胞和免疫纤维细胞；心肌梗塞与其他心血管疾病的异同

高血压是心肌梗塞、中风等心血管疾病的主要原因。心血管纤维化与高血压一起发生，并导致血管阻力、主动脉僵硬和心脏肥大。然而，导致高血压成纤维细胞激活的分子机制仍然很大程度上未知。纤维化有两种类型：替代性纤维化和反应性纤维化。替代性纤维化是由于存活组织的损失而形成疤痕而发生的。反应性纤维化是由于机械和神经激素应激的增加而发生的。尽管这两种类型的纤维化都被认为是适应性过程，但当组织损失太大或压力持续存在时，它们就会变得不适应。肌成纤维细胞代表活化的成纤维细胞的亚群，其已获得收缩功能以促进伤口愈合。因此，肌成纤维细胞是促进替代性纤维化的关键细胞类型。尽管肌成纤维细胞被认为是参与反应性纤维化的成纤维细胞，但最近的实验证据表明，心血管反应性纤维化中存在不同的成纤维细胞群体。因此，我们将利用各种谱系追踪和单细胞 RNA 测序研究的新知识，讨论成纤维细胞亚群的最新定义、调节机制及其在心血管病理生理学中的潜在作用。在成纤维细胞亚群中，我们将重点介绍基质纤维细胞和免疫纤维细胞在心血管纤维化中的新作用，包括高血压、压力超负荷、心肌梗死、动脉粥样硬化、主动脉瘤和肾硬化的实验模型。对这些成纤维细胞亚群分化和激活所涉及的分子机制的探索可能会带来针对与高血压和其他心血管疾病相关的终末器官损伤的新疗法。