sRAGE and early signs of cardiac target organ damage in mild hypertensives

Maresca, Andrea Maria; Guasti, Luigina; Beigrezaei, Sara; Mongiardi, C.; Tandurella, N.; Corso, Rossana; Zerba, Francesco G.; Squizzato, Alessandro; Campiotti, Leonardo; Dentali, Francesco; Klersy, Catherine; Grandi, Anna Maria; Falcone, Colomba

doi:10.1186/s12933-019-0821-5

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…Tetranectin engages in thrombolysis by binding to fibrin and converting plasminogen to plasmin, therefore lower levels of tetranectin could lead to higher rates of thrombosis [ 33 ]. Tetranectin and sRAGE have been reported to be associated with lower all-cause mortality risk and our study further highlights their potential protective effects with regard to the lungs [ 11 , 34 ].…”

Section: Discussionsupporting

confidence: 64%

Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community

et al. 2022

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Rationale It has been speculated that shared mechanisms underlie respiratory and cardiovascular diseases (CVD) including systemic inflammation or mutual risk factors. In this context, we sought to examine the associations of CVD-related plasma proteins with lung function as measured by spirometry in a large community-based cohort of adults. Methods The study included 5777 Framingham Heart Study participants who had spirometry and measurement of 71 CVD-related plasma proteins. The association of plasma proteins with lung function was assessed cross-sectionally and longitudinally using models accounting for familial correlations. Linear mixed models were used for the following measurements: FEV1%predicted, FVC%predicted, and FEV1/FVC ratio with secondary analyses examining obstructive and restrictive physiology at baseline and their new onset during follow up. Measurements and main results Among the 71 CVD-related plasma proteins, 13 proteins were associated in cross-sectional analyses with FEV1%predicted, 17 proteins were associated with FVC%predicted, and 1 protein was associated with FEV1/FVC. The proteins with the greatest inverse relations to FEV1%predicted and FVC%predicted included leptin, adrenomedullin, and plasminogen activator inhibitor-1; in contrast there were three proteins with positive relations to FEV1%predicted and FVC%predicted including insulin growth factor binding protein 2, tetranectin, and soluble receptor for advanced glycation end products. In longitudinal analyses, three proteins were associated with longitudinal change in FEV1 (ΔFEV1) and four with ΔFVC; no proteins were associated with ΔFEV1/FVC. Conclusion Our findings highlight CVD-related plasma proteins that are associated with lung function including markers of inflammation, adiposity, and fibrosis, representing proteins that may contribute both to respiratory and CVD risk.

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Section: Discussionsupporting

confidence: 64%

Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community

et al. 2022

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“…More DM patients used statins, beta-blockers and angiotensin converting enzyme (ACE) inhibitors compared to subjects from the nonDM group (all p < 0.05; Table 1). The median time of DM duration was 11 [7][8][9][10][11][12][13][14][15][16][17][18] years, and DM patients had 44.2% higher glucose, 25.9% higher HbA1c, and 16.4% higher fructosamine levels compared to nonDM subjects (all p < 0.05; Table 1). DM patients were also characterized by slightly poorer renal function (Table 1).…”

Section: Resultsmentioning

confidence: 98%

“…Moreover, Hofmann et al [16] have shown in model using RAGE knock-out mice that both AGEs and RAGE are involved in the aortic leaflets calcification and subsequent AS. Low levels of both sRAGE and endogenous secretory receptor for RAGE (esRAGE), which are considered to be protective against AGEs, were shown as a very early marker of initial target organ damage in mild hypertensives [17] or a factor associated with negative coronary artery remodeling in diabetics [18]. Moreover, the concentration of sRAGE has been associated with increased arterial wall stiffening over time [19].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Kopytek

Ząbczyk

Mazur

et al. 2020

Cardiovasc Diabetol

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Background: Accumulation of advanced glycation end products (AGEs) leads to chronic glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). We aimed to evaluate whether increased accumulation of AGEs in patients with aortic stenosis (AS) and concomitant type 2 diabetes (DM) is associated with AS severity. Methods: We prospectively enrolled 76 patients with severe AS (47.1% males; nonDM), aged 68 [66-72] years, and 50 age-matched DM patients with a median blood glucose level of 7.5 [5.9-9.1] mM and glycated hemoglobin (HbA1c) of 6.8 [6.3-7.8]%, scheduled for aortic valve replacement. Valvular expression of AGEs, AGEs receptor (RAGE), interleukin-6 (IL-6), and reactive oxygen species (ROS) induction were evaluated ex vivo by immunostaining and calculated as the extent of positive immunoreactive areas/total sample area. Plasma levels of AGEs and soluble RAGE (sRAGE) were assessed by ELISAs. Results: Subjects with DM had increased valvular expression of both AGEs (6.6-fold higher, 15.53 [9.96-23.28]%) and RAGE (1.8-fold higher, 6.8 [4.9-8.45]%) compared to nonDM patients (2.05 [1.21-2.58]% and 2.4 [1.56-3.02]%, respectively; both p < 0.001). Plasma levels of AGEs (12-fold higher) and sRAGE (1.3-fold higher) were elevated in DM patients, compared to nonDM (both p < 0.0001). The percentage of valvular ROS-positive (2.28 [1.6-3.09] vs. 1.15 [0.94-1.4]%, p < 0.0001) but not IL-6-positive areas was higher within DM, compared to nonDM valves. In DM patients, the percentage of valvular AGEs-and RAGE-positive areas correlated with HbA1c (r = 0.77, p < 0.0001 and r = 0.30, p = 0.034). Similarly, plasma AGEs and sRAGE levels were associated with HbA1c in the DM group (r = 0.32, p = 0.024 and r = 0.33, p = 0.014, respectively). In all DM patients, we found an association between the amount of valvular AGEs and the disease severity measured as aortic valve area (AVA; r = 0.68, p < 0.0001). Additionally, in DM patients with HbA1c > 7% (n = 24, 48%) we found that valvular expression of AGEs correlated with mean transvalvular pressure gradient (PG mean ; r = 0.45, p = 0.027). Plasma AGEs levels in the whole DM group correlated with AVA (r = − 0.32, p = 0.02), PG mean (r = 0.31, p = 0.023), and PG max (r = 0.30, p = 0.03). Conclusions: Our study suggests that poorly-controlled diabetes leads to increased AGEs and RAGE valvular accumulation, which at least partially, might result in AS progression in DM patients.

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“…First, chronic inflammation was observed in individuals with higher HOMA-IR [ 14 ], which may deteriorate LV systolic function [ 26 ]. Indeed, a recent study demonstrated a significant association between soluble receptor for advanced glycation end products (sRAGE), as a marker related to inflammation, and LV remodeling [ 27 ]. Second, activation of the renin angiotensin system accompanied by elevated HOMA-IR [ 28 ] might cause reduced LVGLS [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community

Hirose

Nakanishi

Daimon

et al. 2021

Cardiovasc Diabetol

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Background Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. Methods We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> − 16.65%). Results Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300). Conclusions In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.

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sRAGE and early signs of cardiac target organ damage in mild hypertensives

Cited by 9 publications

References 36 publications

Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community

Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community

Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community

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