The Severity of Oxygen Desaturation Is Predictive of Carotid Wall Thickening and Plaque Occurrence

Baguet, Jean-Philippe; Hammer, Laure; Lévy, Patrick; Pierre, Hélène; Launois, Sandrine; Mallion, Jean-Michel; Pépin, Jean‐Louis

doi:10.1378/chest.128.5.3407

Cited by 190 publications

(150 citation statements)

References 31 publications

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“…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%

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: 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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“…It has been extensively demonstrated both in animals [3] and humans [4] that IH is a determinant of cardiovascular morbidity. Surprisingly, a decline in mortality rates with age has been observed in OSA patients [5], which suggests a possible cardiovascular protection by IH [6].…”

Section: Introductionmentioning

confidence: 99%

Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2

Béguin

Belaidi

Godin‐Ribuot

et al. 2007

Journal of Molecular and Cellular Cardiology

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. Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2.. Journal of Molecular and Cellular Cardiology, Elsevier, 2007, 42 (2) AbstractObjective. We previously reported that acute intermittent hypoxia (IH) confers delayed cardioprotection against a prolonged ischemic insult in the rat, via the involvement of nitric oxide synthase and K ATP channels. In the present study, we investigated the role of protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), stress activated p38 MAP kinase (MAPK) and extracellular signal regulated kinase (ERK1/2) using selective inhibitors of these pathways. Methods. Adult male rats were exposed to 1-min cycles of IH (10% O 2 , 40 sec) / normoxia (21% O 2 , 20 sec) during 4 hrs or to normoxic cycles. 24 hrs later, isolated hearts were perfused in Langendorff mode and subjected to a 30-min global ischemia followed by 120 min of reperfusion. Results. Compared to normoxic conditions, IH significantly reduced infarct size (22.2  2.4% vs 33.8  2.6%, p<0.05), improved coronary flow and decreased the contracture at reperfusion. When administered before sustained ischemia, chelerythrine (a PKC inhibitor) abolished both the IH-induced reduction in infarct size (36.1  4.9%) and improvement in hemodynamic parameters. In contrast, chelerythrine administration 10 min before IH, did not modify the delayed cardioprotective response. Similarly, wortmannin (a PI3K inhibitor) administration 10 min before IH was unable to block the cardioprotective effects. However, administration of SB203580 (a p38 MAPK inhibitor) and PD98059 (an Erk1/2 inhibitor), 30 min before IH abolished its delayed infarct-sparing effect (32.2  3.4% and 33.9  2.9% respectively). In addition, 24 hrs after IH, a significant increase in p38 MAPK and Erk1/2 phosphorylation was observed by Western blot. Conclusion. These results suggest that the delayed preconditioning induced by intermittent hypoxia does not involve the PI3K signalling pathway and that is mediated by PKC and triggered by p38 MAPK and Erk1/2.

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“…KEYWORDS: C-reactive protein, elderly, hypoxaemia, inflammation, sleep apnoea O bstructive sleep apnoea syndrome (OSAS) is a highly prevalent disorder affecting 2-4% of the general population and is considered an independent risk factor for cardiovascular diseases [1-3], particularly hypertension, coronary artery disease, heart failure and stroke [4,5]. Furthermore, newly diagnosed OSAS patients, free of classical cardiovascular risk factors, such as hypertension, diabetes and smoking, may have early signs of atherosclerosis [6]. Although the pathophysiology of cardiovascular risk is mutifactorial, sympathetic hypertonia [7], endothelial dysfunction [8, 9] and insulin resistance [10] have been postulated as factors initiating and sustaining inflammatory microvascular alterations and therefore atherosclerosis [11,12].…”

mentioning

confidence: 99%

“…Furthermore, newly diagnosed OSAS patients, free of classical cardiovascular risk factors, such as hypertension, diabetes and smoking, may have early signs of atherosclerosis [6]. Although the pathophysiology of cardiovascular risk is mutifactorial, sympathetic hypertonia [7], endothelial dysfunction [8,9] and insulin resistance [10] have been postulated as factors initiating and sustaining inflammatory microvascular alterations and therefore atherosclerosis [11,12].…”

mentioning

confidence: 99%

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly

Roche¹,

Jm²,

Pichot³

et al. 2009

Eur Respir J

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Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown.In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation ,90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI .10 events?h -1 .CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI .10 events?h -1 was the strongest predictor of raised CRP level.The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity. KEYWORDS: C-reactive protein, elderly, hypoxaemia, inflammation, sleep apnoea O bstructive sleep apnoea syndrome (OSAS) is a highly prevalent disorder affecting 2-4% of the general population and is considered an independent risk factor for cardiovascular diseases [1-3], particularly hypertension, coronary artery disease, heart failure and stroke [4,5]. Furthermore, newly diagnosed OSAS patients, free of classical cardiovascular risk factors, such as hypertension, diabetes and smoking, may have early signs of atherosclerosis [6]. Although the pathophysiology of cardiovascular risk is mutifactorial, sympathetic hypertonia [7], endothelial dysfunction [8, 9] and insulin resistance [10] have been postulated as factors initiating and sustaining inflammatory microvascular alterations and therefore atherosclerosis [11,12]. In middle-aged OSAS patients, C-reactive protein (CRP), a marker of inflammation in atherosclerotic lesions [13], is elevated in severe cases [14] and decreases after treatment with nasal continuous positive airway pressure [15]. Despite the putative role of CRP in cardiovascular risk in OSAS, studies conducted to date have yielded contradictory results, with some showing an independent association with disease severity in adults [16][17][18][19] and children [20,21], and others showing no relationship [22,23]. Moreover, the association between obesity and CRP [24] raised the question as to whether elevated CRP reflects the effects of obesity or whether it is specific to OSAS itself.In the elderly, the prevalence of sleep-disordered breathing (SDB) is estimated to be higher than in middle-aged subjects. AN...

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The Severity of Oxygen Desaturation Is Predictive of Carotid Wall Thickening and Plaque Occurrence

Cited by 190 publications

References 31 publications

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

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

Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly

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