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Vascular Pharmacology

Maria Rosa Montinari, Sergio Minelli, Raffaele De Caterina
Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone - who first described their antipyretic effects - and continued in the 19th century with many researchers involved in their extraction and chemical synthesis...
November 1, 2018: Vascular Pharmacology
Jason L Johnson
Cardiovascular diseases encompassing atherosclerosis, aortic aneurysms, restenosis, and pulmonary arterial hypertension, remain the leading cause of morbidity and mortality worldwide. In response to a range of stimuli, the dynamic interplay between biochemical and biomechanical mechanisms affect the behaviour and function of multiple cell types, driving the development and progression of cardiovascular diseases. Accumulating evidence has highlighted microRNAs (miRs) as significant regulators and micro-managers of key cellular and molecular pathophysiological processes involved in predominant cardiovascular diseases, including cell mitosis, motility and viability, lipid metabolism, generation of inflammatory mediators, and dysregulated proteolysis...
October 31, 2018: Vascular Pharmacology
Wen-Tao Sun, Xiang-Chong Wang, Aleksandra Novakovic, Jun Wang, Guo-Wei He, Qin Yang
OBJECTIVES: We recently reported the involvement of ER stress-mediated BKCa channel inhibition in homocysteine-induced coronary dilator dysfunction. In another study, we demonstrated that tetramethylpyrazine (TMP), an active ingredient of the Chinese herb Chuanxiong, possesses potent anti-ER stress capacity. The present study investigated whether TMP protects BKCa channels from homocysteine-induced inhibition and whether suppression of ER stress is a mechanism contributing to the protection...
October 30, 2018: Vascular Pharmacology
Ciro Indolfi, Claudio Iaconetti, Clarice Gareri, Alberto Polimeni, Salvatore De Rosa
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are crucial in vascular remodeling. They exert pivotal roles in the development and progression of atherosclerosis, vascular response to injury, and restenosis after transcatheter angioplasty. As a witness of their importance in the cardiovascular system, a large body of evidence has accumulated about the role played by micro RNAs (miRNA) in modulating both VSMCs and ECs. More recently, a growing number of long noncoding RNA (lncRNAs) came beneath the spotlights in this research field...
October 24, 2018: Vascular Pharmacology
Egidio Imbalzano, Marco Vatrano, Lorenzo Ghiadoni, Giuseppe Mandraffino, Andrea Dalbeni, Bijoy K Khandheria, Rossella Costantino, Giovanni Trapani, Roberta Manganaro, Maurizio Cusmà Piccione, Scipione Carerj, Roberto Ceravolo, Antonino Saitta, Concetta Zito
BACKGROUND: We examined the relative impact of arterial stiffness on the presence and/or severity of chronic mitral regurgitation (MR) in hypertensive patients. METHODS: We prospectively enrolled 141 untreated hypertensive patients (mean age 56.6 ± 11.5 years): 94 with MR, 47 without MR. As a measure of arterial stiffness, pulse wave velocity (PWV) was assessed by applanation tonometry. Assessment of MR severity was obtained through calculation of effective regurgitant orifice area (EROA) and vena contracta by standard two-dimensional transthoracic echocardiography...
October 22, 2018: Vascular Pharmacology
Johanna P Laakkonen, Johanna Lähteenvuo, Suvi Jauhiainen, Tommi Heikura, Seppo Ylä-Herttuala
Vascular endothelial growth factors regulate vascular and lymphatic growth. Dysregulation of VEGF signaling is connected to many pathological states, including hemangiomas, arteriovenous malformations and placental abnormalities. In heart, VEGF gene transfer induces myocardial angiogenesis. Besides vascular and lymphatic endothelial cells, VEGFs affect multiple other cell types. Understanding VEGF biology and its paracrine signaling properties will offer new targets for novel treatments of several diseases.
October 17, 2018: Vascular Pharmacology
Marcela M Blascke de Mello, Juliana M Parente, Richard Schulz, Michele M Castro
Hypertension is characterized by maladaptive vascular remodeling and enhanced oxidative stress in the vascular wall. Peroxynitrite may directly activate latent matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMC) by its S-glutathiolation. MMP-2 may then proteolyze calponin-1 in aortas from hypertensive animals, which stimulates VSMC proliferation and medial hypertrophy. Calponin-1 is an intracellular protein which helps to maintain VSMC in their differentiated (contractile) phenotype. The present study therefore investigated whether aortic MMP-2 activity is increased by oxidative stress in early hypertension and then contributes to hypertrophic arterial remodeling by reducing the levels of calponin-1...
October 16, 2018: Vascular Pharmacology
Dingyuan Tian, Xi Zeng, Weisen Wang, Zhi Wang, Yi Zhang, Yun Wang
Neointima hyperplasia is one of the predominant features of cardiovascular diseases such as atherosclerosis, and is also responsible for the restenosis of vascular surgery including arteriovenous fistula and stent implantation. Endothelial-to-mesenchymal transition (EndMT) contributes to neointima hyperplasia by activation of the Notch or TGF-β signaling pathway. Rapamycin has been utilized as anti-restenosis drug due to its anti-proliferative activity. However, its effects on the EndMT have not been investigated yet...
October 15, 2018: Vascular Pharmacology
M S Vieira-Rocha, P Rodríguez-Rodríguez, J B Sousa, M C González, S M Arribas, A L López de Pablo, C Diniz
Fetal stress increases the susceptibility to cardiovascular diseases in adult age, including hypertension, a process known as fetal programming of hypertension (FPH). This study intends to investigate the interplay between vascular sympathetic nervous system (SNS) and RAS, namely the neuromodulatory role exerted by Angiotensin II (Ang II) receptor-1 (AT1) in FPH, and respective contribution for hypertension. METHODS: 6-month old Sprague-Dawley offspring from mothers fed ad-libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used...
October 13, 2018: Vascular Pharmacology
Sandeep Kumar, Darian Williams, Sanjoli Sur, Jun-Yao Wang, Hanjoong Jo
Atherosclerosis is the primary underlying cause of myocardial infarction, ischemic stroke, and peripheral artery disease. The disease preferentially occurs in arterial regions exposed to disturbed blood flow, in part, by altering expression of flow-sensitive coding- and non-coding genes. In this review, we summarize the role of noncoding RNAs, [microRNAs (miRNAs) and long noncoding RNAs(lncRNAs)], as regulators of gene expression and outline their relationship to the pathogenesis of atherosclerosis. While miRNAs are small noncoding genes that post-transcriptionally regulate gene expression by targeting mRNA transcripts, the lncRNAs regulate gene expression by diverse mechanisms, which are still emerging and incompletely understood...
October 7, 2018: Vascular Pharmacology
Giovanni Cimmino, Roberta Tarallo, Stefano Conte, Andrea Morello, Grazia Pellegrino, Francesco S Loffredo, Gaetano Calì, Nicola De Luca, Paolo Golino, Bruno Trimarco, Plinio Cirillo
INTRODUCTION: Platelets activation/aggregation with subsequent thrombus formation is the main event in the pathophysiology of acute coronary syndrome. Once activated, platelets show an extensive cytoskeleton rearrangement that leads to recruitment of additional platelets to finally cause haemostatic plug formation. Thus, the cytoskeleton plays a pivotal role in this phenomenon. Colchicine (COLC) is an anti-inflammatory drug proven to reduce major cardiovascular events in patients with coronary artery disease...
October 1, 2018: Vascular Pharmacology
Ruslan Hlushchuk, David Haberthür, Valentin Djonov
Therapeutic modulation of angiogenesis is believed to be a prospective powerful treatment strategy to modulate the microcirculation and therefore help millions of patients with cardiovascular and cancer diseases. The often-frustrating results from late-stage clinical studies indicate an urgent need for improved assessment of the pro- and anti-angiogenic compounds in preclinical stage of investigation. For such a proper assessment, detailed vascular visualization and adequate quantification are essential. Nowadays, there are few imaging modalities available, but none of them provides non-destructive 3D-visualization of the vasculature down to the capillary level...
September 22, 2018: Vascular Pharmacology
Sara Rattik, Polyxeni T Mantani, Ingrid Yao Mattisson, Irena Ljungcrantz, Lena Sundius, Harry Björkbacka, Manuela Terrinoni, Michael Lebens, Jan Holmgren, Jan Nilsson, Maria Wigren, Gunilla Nordin Fredrikson
OBJECTIVE: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis...
September 19, 2018: Vascular Pharmacology
Hassan Dehaini, Manal Fardoun, Haissam Abou-Saleh, Ahmed El-Yazbi, Assaad A Eid, Ali H Eid
Cardiovascular disease (CVD) continues to be the leading cause of death worldwide. The effect of estrogen on these diseases has been assessed in in vitro and in vivo models, as well as in observational studies. Collectively, these studies alluded to a cardiovasculo-protective effect of estrogen. However, comprehensive clinical investigation failed to produce concrete proof of a cardiovascular protective effect for hormone replacement therapy (HRT), let alone rule out potential harm. These seemingly paradoxical effects of estrogen were explained by the 'theory of timing and opportunity'...
September 15, 2018: Vascular Pharmacology
Mateusz Tomczyk, Izabela Kraszewska, Jozef Dulak, Agnieszka Jazwa-Kusior
Upon myocardial infarction (MI) immune system becomes activated by extensive necrosis of cardiomyocytes releasing intracellular molecules called damage-associated molecular patterns. Overactive and prolonged immune responses are likely to be responsible for heart failure development and progression in patients surviving the ischemic episode. Heme oxygenase-1 (HO-1) plays a crucial role in heme degradation and in this way releases carbon monoxide, free iron, and biliverdin. This stress-inducible enzyme is induced by various oxidative and inflammatory signals...
September 10, 2018: Vascular Pharmacology
Damian Kloska, Aleksandra Kopacz, Aleksandra Piechota-Polanczyk, Witold Nowak, Jozef Dulak, Alicja Jozkowicz, Anna Grochot-Przeczek
Aging is the most critical risk factor for the development of cardiovascular diseases and their complications. Therefore, the fine-tuning of cellular response to getting older is an essential target for prospective therapies in cardiovascular medicine. One of the most promising targets might be the transcription factor Nrf2, which drives the expression of cytoprotective and antioxidative genes. Importantly, Nrf2 expression correlates with potential lifespan in rodents. However, the effect of Nrf2 activity in vascular diseases might be ambiguous and strongly depend on the cell type...
August 28, 2018: Vascular Pharmacology
Natália A Gonzaga, Wanessa M C Awata, Gabriel T do Vale, Katia C Marchi, Jaqueline J Muniz, Jose E Tanus-Santos, Carlos R Tirapelli
AIM: We investigated the consequences of acute ethanol intake on the anti-contractile effect of perivascular adipose tissue (PVAT). METHODS: The effects of a single dose of ethanol (1 g/kg; p.o. gavage) on the vascular function were assessed within 30 min in male Wistar rats. RESULTS: Ethanol decreased the relaxation induced by acetylcholine and increased the contraction induced by phenylephrine in endothelium-intact, but not in endothelium-denuded aortas without PVAT...
August 26, 2018: Vascular Pharmacology
Gemma Vilahur, Manuel Gutiérrez, Monika Arzanauskaite, Guiomar Mendieta, Soumaya Ben-Aicha, Lina Badimon
Platelets are endowed with a repertoire of surface receptors that enable them to adhere, activate and aggregate upon vascular injury. Platelet adhesion is governed by the interaction between vascular collagen and GPIb-IX-V and GPVI-FcRγ complexes. Platelet kinases downstream 14-3-3ζ-bound GPIb and the FcRγ ITAM domain enable the activation of PLC-γ2 whereas the engagement of soluble agonists (predominantly ADP, TXA2 and thrombin) with Gq-protein coupled receptor trigger PLC-β activation. Once activated, PLC-γ2/β induces the generation of second messengers IP3 and DAG...
August 18, 2018: Vascular Pharmacology
Katarzyna Sztuka, Daria Orszulak-Michalak, Magdalena Jasińska-Stroschein
A systematic review and meta-analysis was performed to test candidate therapeutic approaches in pulmonary hypertension (PH). The efficacy of 522 interventions with >200 unregistered drugs was tested on 7254 animals. We propose a modified formula to assess meta-data that concerns the contribution of PH animal model to the denoted efficacy of tested agents. The measure of efficacy expressed as a response ratio for right ventricle systolic pressure was 0.48 (95% CI, 0.46-0.50; P < 0.00001), mean pulmonary artery pressure was 0...
November 2018: Vascular Pharmacology
P J Hohensinner, J Baumgartner, B Ebenbauer, B Thaler, M B Fischer, K Huber, W S Speidl, J Wojta
BACKGROUND AND AIMS: Macrophages are versatile immune cells involved in tissue degradation and remodeling. Proinflammatory macrophages have the highest capacity of matrix degradation and proteolysis. Within atherosclerotic lesions, proinflammatory macrophages are associated with unstable plaques. Statins have been demonstrated to increase plaque stability. Possible changes of polarized macrophage tissue degradation behavior under statin treatment are currently unknown. METHODS: Polarized macrophages were tested in vitro for matrix degradation capacity with or without statin treatment...
November 2018: Vascular Pharmacology
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