Early Signs of Atherosclerosis in Obstructive Sleep Apnea

Drager, Luciano F.; Bortolotto, Luiz Aparecido; Lorenzi, Maria Cecília; Figueiredo, Adelaide C.; Krieger, E M; Lorenzi-Filho, Geraldo

doi:10.1164/rccm.200503-340oc

Cited by 499 publications

(401 citation statements)

References 57 publications

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“…We further demonstrated that, in addition to the elevation of arterial blood pressure, IH also induces an arterial inflammatory remodeling with subsequent stiffening. These results are consistent with the following: (1) clinical observations demonstrating a significant increase in arterial stiffness in patients with OSA, which correlates with the burden of the disease38, 39; and (2) results in a murine model, in which we previously demonstrated the presence of IH‐induced alterations of vascular mechanical properties (ie, reduced carotid compliance) in rats exposed to 28 days of IH 37. Hypertension and arterial stiffening are closely linked because, although it has been conventionally accepted that hypertension induces arterial stiffening, recent studies also demonstrate that arterial stiffening could precede and contribute to hypertension, therefore establishing a bidirectional relationship.…”

Section: Discussionsupporting

confidence: 91%

“…These data are in accordance with clinical observations, demonstrating a significant increase in the carotid artery intima‐media thickness in patients with OSA that correlates to the severity of nocturnal hypoxemia 38, 39, 41. In rodent models, exposure to at least 14 days of IH resulted in enlarged intima‐media thickness and/or disruption of the elastic network 10, 11, 12, 37, 42, 43.…”

Section: Discussionsupporting

confidence: 90%

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Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

Arnaud

Bouyon

Recoquillon

et al. 2018

JAHA

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BackgroundObstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea–related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH‐induced vascular dysfunctions and inflammatory remodeling.Methods and ResultsTwelve‐week‐old nmMLCK +/+ or nmMLCK −/− mice were exposed to 14‐day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima‐media thickness and an increased expression and activity of inflammatory markers, such as interferon‐γ and nuclear factor‐κB, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH‐induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response.ConclusionsnmMLCK is a key mechanism in IH‐induced vascular oxidative stress and inflammation and both functional and structural remodeling.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

Arnaud

Bouyon

Recoquillon

et al. 2018

JAHA

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“…Moreover, there was a significant positive correlation between cfPWV and AHI. 45 A subsequent study by the same group examined arterial stiffness in OSA patients with and without masked hypertension. 46 It was found that, whereas both types of OSA patients showed significantly higher arterial stiffness as compared to healthy controls, OSA patients with masked hypertension had the highest arterial stiffness.…”

Section: Resultsmentioning

confidence: 99%

“…Out of the seven studies investigating the association between severity of OSA and arterial stiffness, 45,47,48,51,52,60,62 six provided full support for the association 45,47,51,52,60,62 and one provided mixed results. 48 More specifically, the study by Protogerou et al 48 did not find a direct association between OSA severity categories (moderate, severe and very severe) and arterial stiffness.…”

Section: Discussionmentioning

confidence: 99%

Increased arterial stiffness in obstructive sleep apnea: a systematic review

et al. 2010

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Obstructive sleep apnea is a prevalent disease that is associated with significant morbidity and mortality, particularly due to cardiovascular disease. An emerging cardiovascular risk factor, arterial stiffness, may also be involved in the cardiovascular complications of obstructive sleep apnea. The purpose of this review was to summarize the current literature regarding the effect of obstructive sleep apnea on arterial stiffness. We conducted a systematic literature review using PubMed, Embase and the Cochrane Library. We identified 24 studies that met search criteria investigating the effect of obstructive sleep apnea on arterial stiffness. Arterial stiffness was found to be increased in obstructive sleep apnea patients compared with controls or increased in severe compared with mild sleep apnea. In some studies, a positive correlation was identified between the degree of arterial stiffness and sleep apnea severity. In the two randomized, controlled trials and the two nonrandomized trials identified, treatment of obstructive sleep apnea with continuous positive airway pressure led to significant decreases in arterial stiffness. Obstructive sleep apnea appears to have an independent effect on arterial stiffness, which may be one of the mechanisms accounting for sleep apnea-associated cardiovascular risk.

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“…Independently from hypertension and obesity, OSA impairs LV diastolic function, begets LVH, and thus may hasten HFpEF progression 126, 127, 252, 253, 254, 255, 256, 257, 258. Repetitive sleep arousals and hypoxic episodes heighten sympathetic activity and promote endothelial dysfunction, systemic inflammation, and arterial stiffness that may further increase blood pressure and accelerate atherosclerosis progression 128, 259, 260, 261, 262, 263, 264, 265…”

Section: Comorbid Conditionsmentioning

confidence: 99%