Endothelial Dysfunction as an Early Marker of Atherosclerosis: a review of current evidence

Background: Atherosclerosis is a long-term disease that involves the inner layer of your arteries and continues to be one of the most common causes of illness and death around the world. In addition to being a primary cause of coronary artery disease (heart attacks), stroke, and peripheral artery disease, atherosclerosis also causes many other cardiovascular-related illnesses. Historically, atherosclerosis has been viewed as a "fat deposition" or lipid accumulation disorder. (1)(2) However, today, we understand that atherosclerosis is much more than just this. As such, atherosclerosis can now be described as a multifactorial process that includes disturbances in lipid metabolism, chronic inflammation, and vascular dysfunction. The vascular endothelium is critical in maintaining vascular homeostasis.(3)(4) Homeostatic regulation of vascular tone and control over blood flow are two examples of the regulatory functions provided by the endothelium. The endothelium also provides anti-inflammatory and antithrombotic actions via the release of several bioactive molecules, with nitric oxide being the most well-studied molecule released by the endothelium. When functioning properly, the endothelium demonstrates anti-inflammatory action and prevents thrombosis while providing vasodilation. (5)(6) Endothelial dysfunction, on the other hand, is defined as an early and reversible disturbance in endothelial function. These disturbances include decreased availability of nitric oxide, increased levels of reactive oxygen species (oxidative stress), and a pro-inflammatory and prothrombotic state. Because of these characteristics, endothelial dysfunction is generally regarded as the earliest step in the pathogenesis of atherosclerosis prior to structural alterations occurring in the arterial wall.(7)(8) There are numerous cardiovascular risk factors, such as smoking, hypertension, diabetes mellitus, obesity, and dyslipidemia, that lead to endothelial dysfunction. Therefore, identifying endothelial dysfunction at its onset will provide clinicians with significant clinical value because they will then be able to intervene early and prevent further disease progression. Several noninvasive biochemical tests have been developed to measure endothelial function.(9)(10) Therefore, measuring endothelial function can potentially serve as a useful biomarker for detecting early atherosclerotic changes.(11) Aim of the study: The objective of this literature review was to determine whether endothelial dysfunction could be viewed as an early indicator of atherosclerosis. This research focused on assessing recent findings concerning mechanisms contributing to endothelial dysfunction; how it contributes to both the development and progression of atherosclerotic vascular disease; and its clinical implications for early diagnosis.(12)(13) Additionally, this review will summarize the current assessment techniques that are utilized to measure endothelial function and examine their potential utility in identifying those who may have an elevated risk of developing cardiovascular disease.(14)(15) Materials and methods: This review of the literature used a broad electronic database search for all applicable recent science-based literature since 2018. All literature included was limited to articles published by peer-review journals and/or original research. In addition, this review only focused on the relationship between endothelial dysfunction, which is defined as an early indicator of atherosclerosis.(16)(17) The following electronic databases were searched to find these articles: PubMed, Scopus, and Web of Science. A list of keywords that were included in the search include; “endothelial dysfunction,” “early atherosclerosis,” “vascular biomarkers,” “flow mediated dilation,” and “cardiovascular risk factors.”(11)(18) All articles were reviewed and selected based on their relevance to the topic. Only studies written in English, from the past five years (from 2018-2026) and involving human subjects or animal models that are directly related to endothelial dysfunction were included. Any article that dealt with late stage atherosclerosis or other vascular disease was excluded.(13)(14)