Increased platelet alpha 2B -adrenergic receptor gene expression in well-controlled hypertensives: the effect of arterial stiffness

Marketou, Maria; Kontaraki, Joanna; Papadakis, John A.; Vrentzos, G.; Patrianakos, Alexandros; Fragkiadakis, Konstantinos; Tsiverdis, P.; Lempidakis, D.; Chlouverakis, Gregory; Vardas, Panos; Parthenakis, Fragiskos I.

doi:10.1016/j.jash.2017.08.006

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Furthermore, recent preclinical studies underlined the potential of these receptors to safeguard cardiac muscle under adrenergic surge by governing intracellular Ca2 + handling and contractility ( 47 , 48 ), and therefore reduce the risk of HF. α2B receptor stimulation induces also platelet aggregation ( 49 ). This may explain the protective effect of lower activity on the risk of CAD, which was however insufficient to counteract the increase in HF.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure

Baudier,

Fougerousse,

Asselbergs

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThe effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.MethodsGenetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).ResultsLower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74–0.93, P = 0.001) and 0.95 (95% CI 0.93–0.97, P = 8 × 10−6). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05–1.12, P = 3 × 10−7). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92–1.07, P = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.ConclusionsThis study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.

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Section: Discussionmentioning

confidence: 99%

Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure

Baudier,

Fougerousse,

Asselbergs

et al. 2023

Front. Cardiovasc. Med.

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Molecular mechanisms modulating hemostasis and development of acute pyelonephritis after contact ureteral lithotripsy

Barinov

Malinin

2022

Urology reports (St. - Petersburg)

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BACKGROUND: Improving the efficiency and reducing the frequency of complications of surgical treatment of urolithiasis is an actual problem in urology. AIM: To establish the molecular mechanisms that modulate the hemostasis and development of acute pyelonephritis after percutaneous contact ureteral lithotripsy. MATERIALS AND METHODS: The study included 21 patients with urolithiasis and concretions in the upper third of the ureter in whom, after standard lithokinetic therapy for 7 days, according to imaging control data, the calculus did not move from the pyelo-ureteral zone to the middle third of the ureter. All patients underwent contact ureteral lithotripsy. After the operation, nonsteroidal anti-inflammatory drugs and antibiotics were used for 2 days. The severity of hematuria and leukocyturia was assessed 24, 48, and 72 h after contact ureteral lithotripsy. Functional activity receptors were analyzed in vitro on a platelet suspension. Platelet aggregation was assessed by the turbidimetric method using a ChronoLog analyzer (USA). RESULTS: At 24, 48, and 72 h after contact ureteral lithotripsy, a significant decrease was found in the severity of microhematuria (p 0.001). The leukocyturia level decreased over 48 h (p 0.05) and increased 72 h after surgery (p 0.001). The above dynamics of complications after hours indicates that two pathological processes simultaneously develop in the ureteral mucosa: induction of thrombogenesis and modulation of an acute inflammatory reaction. Аfter 24 h of NSAID discontinuation (3 days after contact ureteral lithotripsy), normoreactivity of the 2-adrenergic receptors, GPVI receptors, AT1 receptors, PAF receptors, P2X1 receptors, and A2A receptors was found, as well as hyporeactivity of purine P2Y receptors and 2-adrenergic receptors. The correlation between the severity of hematuria and the activity of GPVI receptors for collagen, 2-adrenergic receptors for adrenaline, and AT1 receptors for angiotensin-2 (p 0.05) makes it possible to specify the possible interaction of platelet receptors that maintain hemostasis during inhibition of the COXTxA2 axis. Maintaining the severity of pyelonephritis after contact ureteral lithotripsy is associated with the interaction of the PAF receptors, purine ionotropic P2X1 receptors, and 2-adrenergic receptors on blood cells. CONCLUSIONS: The analysis of targets receptors on platelets and leukocytes after contact ureteral lithotripsy in the upper third of the ureter with ineffective lithokinetic therapyallows us to outline ways to improve conservative therapy to limit the development of postoperative complications.

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Increased platelet alpha 2B -adrenergic receptor gene expression in well-controlled hypertensives: the effect of arterial stiffness

Cited by 2 publications

References 28 publications

Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure

Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure

Molecular mechanisms modulating hemostasis and development of acute pyelonephritis after contact ureteral lithotripsy

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