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BackgroundObstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.MethodsWe searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE−/−) mice. We used the standardised mean difference (SMD) to compare results between studies.ResultsIH significantly increased mean arterial pressure (+13.90 (95% CI 11.88–15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima–media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58–1.62); absolute values +5.23 (2.81–7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE−/− mice (SMD 1.08 (95% CI 0.80–1.37)).ConclusionsOur meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.

Elastic fibers are extracellular matrix components made of elastin (90%) and microfibrils (10%). Elastin is synthesized primarily in early life and confers to the large elastic arteries the property of elasticity, allowing storage of energy and stroke volume during the systole, then release of energy and blood volume during the diastole. This phenomenon helps to decrease the load on the heart. With aging, elastin is progressively degraded, leading to arterial stiffening and dysfunction. In a previous study we showed that chronic administration of Dill Extract at 5% or 10% v/v administered in drink water could be considered as an anti-aging product for the cardiovascular system but with different pathways. If 5% and 10% DE treatment increased tropoelastin and LOXL1 expressions in the aorta and induced the neo-synthesis of elastic fibers in the aortic wall of DE-treated aged mice and both had a reversal effect on aged related cardiac hypertrophy, surprisingly, blood pressure was decreased only with 5% DE and has no effect on mechanics properties of ascending aorta contrary to 10% DE. So, we decided to investigate further the effect of 5% DE. In this study, we explored the effects on elastin production (Elisa and histology) and large artery elasticity (pressure arteriography) in aged and adult mice of both genders. In opposite of the previous study, we investigate the effect of DE on the abdominal aorta which has different developmental origins, which could explain the different reaction to DE doses. We showed that chronic treatment with dill extract reduced the age-related cardiac hypertrophy only in male mice and re-induced elastic fibers formation, even in aged animals. Moreover, dill extract-treated mice exhibited increased arterial distensibility, especially in female mice. Our results suggest that dill extract presents an interesting potential for arterial function improvement in an anti-aging perspective, even when treating aged animals.

In the arteries of vertebrates, evolution has given rise to resilient macromolecular structures, elastin and elastic fibers, capable of sustaining an elevated blood pressure and smoothening the discontinuous blood flow and pressure generated by the heart. Elastic fibers are produced only during development and childhood, before being progressively degraded by mechanical stress and enzymatic activities during adulthood and aging. During this period, arterial elastic fiber calcification and loading of lipids also occur, all of these events conducting to arteriosclerosis. This leads to a progressive dysfunction of the large elastic arteries inducing elevated blood pressure as well as altered hemodynamics and organ perfusion, which induce more global malfunctions of the body during normal aging. Additionally, some arterial conditions occur more frequently with advancing age, such as atherosclerosis or aneurysms, which are called age-related diseases or pathological aging. The physiological or pathological degradation of elastic fibers and function of elastic arteries seemed to be rather inevitable over time. However, during the recent years, different molecules - including several ATP-dependent potassium channel openers, such as minoxidil - have been shown to re-induce elastin production and elastic fiber assembly, leading to improvements in the arterial structure and function or in organ perfusion. This review summarizes the changes in the arterial elastic fibers and structure from development until aging, and presents some of the potential pharmacotherapies leading to elastic fiber neosynthesis and arterial function improvement.

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase&ndash, like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10% v/v, in drinking water) on the structure and function of the ascending aorta. DE treatment, especially at 10%, of aged mice protected pre-existing elastic lamellae, reactivated tropoelastin and LOXL-1 expressions, induced elastic fiber neo-synthesis, and decreased the stiffness of the aging aortic wall, probably explaining the reversal of the age-related cardiac hypertrophy also observed following the treatment. DE could thus be considered as an anti-aging product for the cardiovascular system.