Review article
Matricellular proteins: Potential biomarkers and mechanistic factors in aortic aneurysms

https://doi.org/10.1016/j.yjmcc.2022.05.001Get rights and content

Highlights

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    Matricellular proteins serve as potential valuable biomarkers of aortic aneurysm diseases.

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    Matricellular proteins are important regulators in aneurysm formation.

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    Matricellular proteins orchestrate pathogenic cellular processes and extracellular matrix remodeling in aneurysm formation.

Abstract

Aortic aneurysms, including thoracic aortic aneurysms and abdominal aortic aneurysms, are life-threatening macrovascular diseases with high mortality. The already known key mechanisms implicated in aortic aneurysm pathogenesis involve the remodeling of the extracellular matrix and a set of cellular responses, such as inflammation, oxidative stress and vascular smooth muscle cell dysfunction. Matricellular proteins constitute a group of nonstructural extracellular proteins that link the interaction between cells and their extracellular microenvironment and have been widely reported in different diseases, including aortic aneurysms. In the present review, we summarize the role of various matricellular proteins in the pathogenesis and progression of aortic aneurysms, as well as address the possibility of using these proteins as biomarkers and pathogenic factors, to highlight their clinical significance in aortic aneurysms.

Introduction

Aortic aneurysms are highly lethal diseases with high mortality, and they are defined as the pathological expansion of aorta that exceeds 50% of the normal vascular diameter[1,2]. Aortic rupture is the most devastating complication of aortic aneurysms, leading to sudden deaths in approximately 60% to 80% of patients[3,4]. Depending on the sites of vasodilation, aortic aneurysms are classified into thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), which are two different diseases. A tendency of familial inheritance due to monogenic mutations is commonly observed in TAA patients, such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos syndrome (vEDS). TAA is further divided into ascending aortic aneurysm and descending aortic aneurysm, which show different pathological patterns due to the distinct origin of smooth muscle cells [5,6]. The pathology of ascending aortic aneurysm is mainly characterized by medial degeneration, while descending aortic aneurysm and AAA, which share the same smooth muscle cell origin, are associated with heavy atherosclerosis and calcification[7]. Unlike TAA, polygenic contributions and a series of risk factors, which include atherosclerosis, cigarette smoking, aging, male sex, etc., are involved in the pathogenesis of AAA[8].

Despite their different sites and etiologies, both TAA and AAA are predominantly hallmarked by the disruption and the remodeling of extracellular matrix (ECM), which directly causes the weakening of the vessel wall. Additionally, the cellular mechanisms are similar in the two types of aortic aneurysms[7,9]. Matricellular proteins are ECM components and important regulators that bridge ECM proteins and intracellular signaling pathways. The involvement of matricellular proteins in aortic aneurysm diseases has been intensively studied. In the current review, the potential roles of each specific matricellular protein in aortic aneurysms are summarized and discussed.

Section snippets

Current understanding of aortic aneurysm pathogenesis

The aortic wall consists of three layers, namely tunica intima, tunica media and tunica adventitia. While a single layer of endothelial cells covered by connective tissue and internal elastic lamina forms tunica intima, tunica media and tunica adventitia are composed of an intricate arrangement of ECM and different vascular cells, including vascular smooth muscle cells (VSMCs) and fibroblasts as constituents, together with some specific infiltrated immune cells under inflammatory conditions.

ECM remodeling: the key pathological characteristic

ECM is the critical structural constituent of the aortic wall and is mainly composed of elastic fibers, various types of collagen, proteoglycans and glycoproteins[69]. Distributed throughout the three layers of the blood vessel wall, ECM proteins not only contribute to aortic elasticity, tensile strength and integrity, but also influence cellular behaviors, thereby maintaining vascular homeostasis[70]. Elastin fragmentation and collagen degradation are critical events in the formation of both

Matricellular proteins

Matricellular proteins constitute a group of proteins that also serve as extracellular matrix components, but differ from classic ECM proteins due to their nonstructural functions that fail to contribute to cell adhesion. The term “matricellular”, coined by Paul Bornstein in the 1990s, was used to describe the dual interaction among cells and their extracellular microenvironment. In diverse physiological (especially early development) and pathological processes, matricellular proteins are

TSPs

TSPs, which were initially found in platelets, comprise a group of calcium-binding glycoproteins with multimeric structures. They are synthesized and secreted by different cell types in addition to platelets, including leukocytes and endothelial cells. The TSP family includes five members, TSP-1 to -5, which are further divided into two subtypes based on their structural homology (TSP-1/2 from subgroup A, and TSP-3/4/5 from subgroup B). Known structural domains of TSP proteins consist of an

Matricellular proteins as potential biomarkers of aortic aneurysms

Currently, the diagnosis and screening for TAA and AAA still largely rely on measuring the aortic size by conventional imaging, such as ultrasonography, computed tomography angiography (CTA) and magnetic resonance imaging (MRI). Of note, the progress of aortic aneurysm shows an asymptomatic, nonlinear and discontinuous pattern, and rapid expansion and rupture occur even in small aneurysms with diameters less than 5.5 cm[244]. Hence, effective biomarkers for TAA and AAA are of great significance

Conclusions and perspectives

Aortic aneurysms are life-threatening diseases for which a thorough understanding is lacking in terms of the mechanism and available medical therapies. Thus, the investigation into the pathogenesis and biomarkers of aortic aneurysms is of great importance. In the current review, we summarized a spectrum of matricellular proteins that have been reported in TAA and AAA. This group of extracellular proteins is induced by different pathogenic stimuli during aortic aneurysm formation. Different from

Disclosures

None.

Acknowledgement

This work was supported by funding from the National Natural Science Foundation of China (NSFC, 81730010, 82100480, 31930056 and 81921001) and China Postdoctoral Science Foundation (2020M680257).

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