Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

2015 ◽  
Vol 114 (09) ◽  
pp. 498-518 ◽  
Author(s):  
Karin Müller ◽  
Madhumita Chatterjee ◽  
Dominik Rath ◽  
Tobias Geisler

SummaryPlatelets play a pivotal role in chronic inflammation leading to progression of atherosclerosis and acute coronary events. Recent discoveries on novel mechanisms and platelet-dependent inflammatory targets underpin the role of platelets to maintain a chronic inflammatory condition in cardiovascular disease. There is strong and clinically relevant crosslink between chronic inflammation and platelet activation. Antiplatelet therapy is a cornerstone in the prevention and treatment of acute cardiovascular events. The benefit of antiplatelet agents has mainly been attributed to their direct anti-aggregatory impact. Some anti-inflammatory off-target effects have also been described. However, it is unclear whether these effects are secondary due to inhibition of platelet activation or are caused by direct distinct mechanisms interfering with inflammatory pathways. This article will highlight novel platelet associated targets that contribute to inflammation in cardiovascular disease and elucidate mechanisms by which currently available antiplatelet agents evolve anti-inflammatory capacities, in particular by carving out the differential mechanisms directly or indirectly affecting platelet mediated inflammation. It will further illustrate the prognostic impact of antiplatelet therapies by reducing inflammatory marker release in recent cardiovascular trials.

2016 ◽  
Author(s):  
Karl Egan ◽  
Fionnuala Ni Ainle ◽  
Dermot Kenny

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).


Author(s):  
Karl Egan ◽  
Fionnuala Ni Ainle ◽  
Dermot Kenny

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. In 2008 alone, 17.3 million deaths (representing 30% of all deaths) were attributable to the complications of cardiovascular disease. Of these deaths, 7.3 million were due to coronary artery disease while 6.2 million were attributable to stroke. Cardiovascular disease is expected to remain the leading cause of death globally, with the number of deaths expected to reach 23.6 million annually by 2030 (WHO statistics, 2012). Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction (MI) and ischemic stroke. Platelets are the key cellular component of arterial thrombi with platelet adhesion under high shear conditions being central to atherothrombosis. In addition, platelets play a role in the progression of atherosclerosis. In this review, we will discuss the evidence for the role of platelets in atherothrombosis, notably the efficacy of antiplatelet agents in the prevention of ischemic events, and finally their role in the progression of atherosclerosis (atherogenesis).


2010 ◽  
Vol 120 (6) ◽  
pp. 219-229 ◽  
Author(s):  
Madhav Lavu ◽  
Shashi Bhushan ◽  
David J. Lefer

H2S (hydrogen sulfide), viewed with dread for more than 300 years, is rapidly becoming a ubiquitously present and physiologically relevant signalling molecule. Knowledge of the production and metabolism of H2S has spurred interest in delineating its functions both in physiology and pathophysiology of disease. Although its role in blood pressure regulation and interaction with NO is controversial, H2S, through its anti-apoptotic, anti-inflammatory and antioxidant effects, has demonstrated significant cardioprotection. As a result, a number of sulfide-donor drugs, including garlic-derived polysulfides, are currently being designed and investigated for the treatment of cardiovascular conditions, specifically myocardial ischaemic disease. However, huge gaps remain in our knowledge about this gasotransmitter. Only by additional studies will we understand more about the role of this intriguing molecule in the treatment of cardiovascular disease.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lucia Cojocaru ◽  
Andrei Constantin Rusali ◽  
Cristina Şuţa ◽  
Anca Mihaela Rădulescu ◽  
Maria Şuţa ◽  
...  

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.


2009 ◽  
Vol 42 (6) ◽  
pp. 449-459 ◽  
Author(s):  
Amanda J Rickard ◽  
Morag J Young

The mineralocorticoid receptor (MR) and glucocorticoid receptor are ligand-activated transcription factors that have important physiological and pathophysiological actions in a broad range of cell types including monocytes and macrophages. While the glucocorticoids cortisol and corticosterone have well-described anti-inflammatory actions on both recruited and tissue resident macrophages, a role for the mineralocorticoid aldosterone in these cells is largely undefined. Emerging evidence, however, suggests that MR signalling may promote pro-inflammatory effects. This review will discuss the current understanding of the role of corticosteroid receptors in macrophages and their effect on diseases involving inflammation, with a particular focus on cardiovascular disease.


2017 ◽  
Vol 24 (4) ◽  
pp. 369-375 ◽  
Author(s):  
Saibal Chakravorty ◽  
Indranil Purkait ◽  
Anil Pareek ◽  
Avinash Talware

AbstractHydroxychloroquine, an antimalarial agent has also been found to possess antidiabetic action. Onset of type-2 diabetes (T2DM) and cardiovascular disease is now considered to be the outcome of systemic inflammation. Many clinical trials are targeting systemic inflammation to reduce cardiovascular risk. Anti-inflammatory drugs with cardiovascular effects may be valuable therapeutic intervention to reduce massive cardiovascular risk in T2DM. In this review, antidiabetic action and potential cardioprotective role of hydroxychloroquine has been discussed. By virtue of its antidiabetic, lipid lowering, anti-platelet, anticoagulant and anti-inflammatory properties, hydroxychloroquine can be a key therapeutic alternative to manage patients with T2DM.


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