Proinflammatory Arterial Stiffness Syndrome: A Signature of Large Arterial Aging

Wang, Mingyi; Monticone, Robert E.; McGraw, Kimberly R.

doi:10.1159/000490244

Cited by 33 publications

(44 citation statements)

References 178 publications

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“…The age-associated increases in arterial elastolysis is linked closely to an increase in arterial calcification [1][2][3][4] . Maintaining certain levels of intact TPELN is a key to ensuring arterial elastic meshwork integrity and arterial health 5,6,13 .…”

Section: Discussionmentioning

confidence: 99%

“…Aging is the major risk factor for quintessential cardiovascular diseases, such as hypertension, due mainly to adverse arterial proinflammatory remodeling [1][2][3] . With advancing age, the arterial wall becomes less resilient and stiffens, resulting mainly from a cascade of the breakdown and calcification of the elastic network, and from the proinflammation of vascular smooth muscle cells (VSMCs) [1][2][3][4][5][6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

“…SM22α is enriched in differentiated VSMCs and increased levels are found in young arterial walls while old show decreased amounts 10,17,20 . Thus, aged VSMCs appear dedifferentiated and proinflammed 1,2 . p38 mitogen-activated protein kinase (p38), a stress-activated dedifferentiated signaling molecule, is increased in aging VSMCs [21][22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

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Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification

Kim

Liu

et al. 2020

Preprint

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ObjectiveThe proinflammatory phenotypic shift of vascular smooth muscle cells (VSMCs) is closely linked to the elastolysis and calcification in the aging arterial wall. Degradation of tropoelastin (TPELN) is a key molecular event which often accompanies the proinflammatory phenotypic shift of VSMCs, arterial elastolysis and calcification with aging. Milk fat globule-EGF factor 8 (MFG-E8), secreted mainly from VSMCs, predominantly binds to degenerated elastin fibers, and alters VSMCs phenotypes. Here, we investigated how MFG-E8 proinflammatory signaling in the arterial wall, in vivo, and VSMCs, in vitro, affects arterial elastolysis and calcification with advancing age.Methods and ResultsIn vivo immunostaining and immunoblotting studies indicated that MFG-E8, elastic lamina breaks, and calcium-phosphorus products were markedly increased while intact TPELN (∼70Kda) protein was dramatically decreased in aortic walls or isolated aortic VSMCs harvested from old (30-month-old) vs. young (8-month-old) Fischer 344 × Brown Norway rats (FXBN). In vitro studies demonstrated that (1) treating either young or old VSMCs to recombinant human MFG-E8 (rhMFG-E8) for 24 hours significantly reduced intact TPLEN levels and this effect was reduced by SB203580, a p38 mitogen-activated protein kinase inhibitor; (2) activated MMP-2 levels were significantly increased in both young and old VSMCs treated with rhMFG-E8, and this activation was also inhibited by SB203580; (3) MMP-2 physically interacted with TPLEN and cleaved intact TPLEN from VSMCs; (4) downregulation of either MFG-E8 or MMP-2 in VSMCs via siRNA significantly increased the levels of intact TPELN; (5) rhMFG-E8 treatment markedly reduced contractile protein, smooth muscle 22-alpha, and anti-calcification protein, fetuin-A, levels in both young and old VSMCs, which were blocked by SB203580. Notably, MMP-2 activity, elastic laminae degeneration, and calcium deposits were significantly increased while fetuin-A levels are markedly decreased in old WT vs. MFG-E8 mice.ConclusionsTaken together, our current findings suggest that MFG-E8, via p38 signaling in VSMCs, promotes MMP-2-associated elastolysis and calcification in the aging arterial wall.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification

Kim

Liu

et al. 2020

Preprint

Self Cite

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“…In contrast with smoking and T2DM patients, the incidence rate of elderly patients peaked in summer. This opposite trend in mortality may be attributed to compromised elasticity of large conductive arteries [44]. Stiffening of the large arteries makes elderly people susceptible to hypovolemia and hypotension [45].…”

Section: Discussionmentioning

confidence: 99%

Seasonal Changes in Incidence of Patients With Diabetes Undergoing Cardiac Surgery

Kovács¹,

Peták²,

Agócs³

et al. 2020

Preprint

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Background: To evaluate the monthly incidence rate of patients with diabetes requiring heart surgery at a tertiary-care university hospital in East-Central Europe with a temperate climate zone. We also assessed whether additional factors affecting small blood vessels (smoking, aging, and diabetes) modulate the seasonal variability of diabetes.Methods: Medical records were retrospectively analyzed for all 9837 consecutive adult patients who underwent surgery at our institution between 2007 and 2018. Individual seasonal variations of diabetes, smoking, and elderly patients were analyzed monthly. Potential additive or subtractive effects of the coexistence of these factors in seasonal changes in incidence rates were also examined. In the absence of a waiting list, incidence rates accurately reflect the frequency of exacerbation of cardiovascular symptoms requiring surgical intervention.Results: Significant seasonal variations in the monthly incidence rate of diabetes (p < 0.02), smoking (p < 0.001), and elderly (p < 0.001) patients were observed at the cardiac surgery unit. The peak incidence of non-elderly and smoking patients with diabetes was during winter, whereas heart surgery in elderly patients without diabetes and smoking was most frequently required in summer. Concomitant occurrence of diabetes and smoking had an additive effect on the relative incidence rate of requirement for cardiac surgery (p < 0.001), while the simultaneous presence of older age and diabetes or smoking eliminated seasonal variations.Conclusions: Scheduling regular cardiovascular control in accordance with periodicities in diabetes, elderly, and smoking patients more than once a year may improve patient health and social consequences.Trial registration: NCT03967639

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“…Cardiovascular disease is the leading cause of death in many developed countries. Large elastic artery stiffening is an independent predictor of future CVD diagnosis and likely are responsible for the development of CVD in older adults [23,24]. Arterial hypertension is a common disease with great harm.…”

Section: Discussionmentioning

confidence: 99%

Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

Xu¹,

Pan²,

Chen³

et al. 2019

Artery Res

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A B S T R A C TBackground: Cathepsin L (Cat L) is involved in the regulation of vascular aging processes. The aim of this study was to evaluate the relationship between plasma Cat L level and arterial stiffness marker through brachial-ankle pulse wave velocity (baPWV) in geriatric patients. Methods:Cross-sectional study with 502 people were selected from a population of 2250 people aged over 65 years old, from three different basic health zones of Shanghai. Blood samples were collected, and the baPWV was measured with the SphygmoCor system. The geriatric patients with baPWV values >20 m/s were defined as the high arterial stiffness group.Results: In total, 248 (49.4%) of the 502 geriatric patients in this study were in the high arterial stiffness group. The high arterial stiffness group were older (p = 0.006) and had higher prevalence of hypertension (p = 0.020), coronary heart disease (CHD) (p = 0.037), higher systolic blood pressure (SBP) (p = 0.018), pulse pressure (p = 0.017), plasma Cat L (p = 0.002) and logarithmically transformed C-reactive protein (p = 0.023) levels than those in the low arterial stiffness group. Multivariable forward stepwise regression analysis showed that Cat L (b = 0.418, p = 0.011) and hypertension (b = 0.217, p = 0.029) were associated with baPWV values in geriatric patients. Moreover, an increased plasma Cat L level (odds ratio (OR): 1.048; 95% confidence interval (CI): 1.043-1.169; p = 0.018) was an independent factor for arterial stiffness among the geriatric patients. Conclusion:In this study, plasma Cat L level was positively correlated with arterial stiffness in geriatric patients.

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Proinflammatory Arterial Stiffness Syndrome: A Signature of Large Arterial Aging

Cited by 33 publications

References 178 publications

Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification

Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification

Seasonal Changes in Incidence of Patients With Diabetes Undergoing Cardiac Surgery

Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

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