Kasal DA, Sena V, Huguenin GVB, De Lorenzo A, Tibirica E. Microvascular endothelial dysfunction in vascular senescence and disease. Front Cardiovasc Med. 2025 Feb 18;12:1505516. doi: 10.3389/fcvm.2025.1505516. PMID: 40041173; PMCID: PMC11878104.
Abstract
Cardiovascular disease (CVD) is the main cause of morbidity and mortality in the adult and the elderly, with increasing prevalence worldwide. A growing body of research has focused on the earliest stage of vascular decline-endothelial dysfunction (ED)-which at the microvascular level can anticipate in decades the diagnosis of CVD. This review aims to provide a prospect of the literature regarding the development of ED as an indissociable feature of the aging of the cardiovascular system, highlighting the role of inflammation in the process. Vascular aging consists of a lifelong continuum, which starts with cell respiration and its inherent production of reactive oxygen species. Molecular imbalance is followed by cellular epigenetic changes, which modulate immune cells, such as macrophage and lymphocyte subtypes. These mechanisms are influenced by lifestyle habits, which affect inflammation hotspots in organism, such as visceral fat and gut microbiota. The process can ultimately lead to an environment committed to the loss of the physiological functions of endothelial cells. In addition, we discuss lifestyle changes targeting the connection between age-related inflammation and vascular dysfunction. Addressing microvascular ED represents a critical endeavor in order to prevent or delay vascular aging and associated diseases.
Conclusions
Oxidative stress and inflammation are inherent to vascular aging, act through the lifespan of animals, and are probably set since intrauterine development. Mechanisms essential to homeostasis, depending on the local molecular environment and concentration, can become deleterious and induce ED. Both suppressing proinflammatory and enhancing anti-inflammatory pathways in vasculature are promising targets for treatments aiming to mitigate age-related vascular dysfunction and disease. Gut microbiota is an important milieu where a chronic inflammatory state can convey the progression of vascular decline, but also suitable to interventions through nutritional strategies. Regular physical activity has also been proved in multiple studies to reduce inflammation and ED in both young and the elderly, regardless of the intensity. The vast range of mechanisms coexisting in aging and CVD, and which initially cause ED, is summarized in Figure 1. There is extensive experimental and clinical evidence to support the concept that both microvascular network alterations and tissue perfusion defects may precede and predict the development of cardiovascular and metabolic diseases. Moreover, the functional and subsequent structural alterations in both microvascular reactivity and density, as well as the alterations in the macrocirculation characteristic of physiologic vascular aging, contribute to the development of target end-organ damage (148). Therefore, the microcirculation may be considered an essential target of both the pharmacological and the non-pharmacological treatment of arterial hypertension and other CVD (148).
Keywords: aging; cardiovascular disease; inflammation; microvascular endothelial dysfunction; oxidative stress.
148. de Moraes R, Tibirica E. Early functional and structural microvascular changes in hypertension related to aging. Curr Hypertens Rev. (2017) 13(1):24–32. doi: 10.2174/1573402113666170413095508
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