The Experts below are selected from a list of 5388 Experts worldwide ranked by ideXlab platform
Garret A. Fitzgerald - One of the best experts on this subject based on the ideXlab platform.
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The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs.
Trends in pharmacological sciences, 2017Co-Authors: Tilo Grosser, Emanuela Ricciotti, Garret A. FitzgeraldAbstract:The principal molecular mechanisms underlying the Cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and their relative predisposition to complications. In review article, we discuss how heterogeneity in the pharmacokinetics and pharmacodynamics of distinct NSAIDs may be expected to affect their CV risk profile. We consider evidence afforded by studies in model systems, mechanistic clinical trials, a meta-analysis of randomized controlled trials, and two recent large clinical trials, Standard Care vs. Celecoxib Outcome Trial (SCOT) and Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION), designed specifically to compare the CV safety of the cyclooxygenase-2-selective NSAID, celecoxib, with traditional NSAIDs. We conclude that SCOT and PRECISION have apparently not compared equipotent doses and have other limitations that bias them toward underestimation of the relative risk of celecoxib.
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Cardiovascular Pharmacology of nonselective nonsteroidal anti inflammatory drugs and coxibs clinical considerations
American Journal of Cardiology, 2002Co-Authors: Garret A. FitzgeraldAbstract:Cyclooxygenase (COX)-2 inhibitors have been developed with the goal of providing similar efficacy and greater safety compared with traditional nonsteroidal anti-inflammatory drugs. Development was based on the hypothesis that COX-1 is the housekeeping enzyme necessary for production of prostaglandins (PGs) with homeostatic functions, whereas COX-2 is a mediator of pathophysiologic processes. However, later research has demonstrated a role of COX-2 in production of PGs that have functions under normal physiologic conditions. In the vasculature, COX-2 seems to be the main enzyme responsible for the production of prostacyclin. Increased synthesis of this vasodilatory and antithrombotic PG represents a homeostatic response during periods of accelerated platelet-vessel wall interactions and counteracts increased synthesis of COX-1-derived prothrombotic prostanoid thromboxane A2 (TXA2). The clinical sequelae of inhibiting prostacyclin activity in the absence of concomitant inhibition of TXA2 are not currently clear. Animal studies show that inhibition of prostacyclin activity does not lead to spontaneous thrombosis but may increase response to thrombotic stimuli. Therefore, prostacyclin synthesis may be important for limiting thrombotic events in patients who are at an increased Cardiovascular risk. Overviews of clinical studies in arthritis and Alzheimer’s disease have not demonstrated increased Cardiovascular risk associated with specific COX-2 inhibition in most patients. However, data from 1 clinical trial revealed a 5-fold divergence in rates of myocardial infarction between a coxib and a nonsteroidal anti-inflammatory drug comparitor. Credible explanations for the results of this trial have been proposed and further studies are necessary to clarify the relative risk-to-benefit ratio of COX-2 inhibition in patients at increased risk for Cardiovascular events, and the effects of concomitant aspirin therapy.
Randal A Skidgel - One of the best experts on this subject based on the ideXlab platform.
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Bradykinin-Degrading Enzymes: Structure, Function, Distribution, and Potential Roles in Cardiovascular Pharmacology
Journal of Cardiovascular Pharmacology, 1992Co-Authors: Randal A SkidgelAbstract:Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24. 15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well
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Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in Cardiovascular Pharmacology.
Journal of cardiovascular pharmacology, 1992Co-Authors: Randal A SkidgelAbstract:Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24.15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well. Because bradykinin is inactivated (for binding the B2 receptor) when any of its peptide bonds are cleaved, all of these enzymes qualify as potential "kininases" in vivo; however, the importance of a particular enzyme as a kininase will depend on its localization, access to bradykinin, and the presence of other peptidases. In addition, these peptidases can cleave a variety of other peptide hormone substrates. Determination of the importance of a peptidase in the inactivation of bradykinin during a particular physiological response can be difficult, but specific peptidase inhibitors and kinin receptor antagonists are useful tools in investigating these questions.
Teresa Tejerina - One of the best experts on this subject based on the ideXlab platform.
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TGF-beta1: a novel target for Cardiovascular Pharmacology.
Cytokine & growth factor reviews, 2007Co-Authors: Santiago Redondo, Carlos G Santos-gallego, Teresa TejerinaAbstract:Transforming growth factor beta-1 (TGF-beta1) plays a key role in Cardiovascular disease by a process which allows the loss of its protective properties. The first therapeutic attempt to restore its function by selectively designed novel drugs are being made. In addition, it has been recognized that the TGF-beta1 pathway is involved in the vascular mechanism of action of some current clinical drugs, such as acetylsalicylic acid, thiazolidinediones and statins. The aim of this paper is to review the possible value of TGF-beta1 as both a disease marker and a therapeutical target for Cardiovascular disease.
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TGF-β1: a novel target for Cardiovascular Pharmacology
Cytokine & Growth Factor Reviews, 2007Co-Authors: Santiago Redondo, Carlos G Santos-gallego, Teresa TejerinaAbstract:Abstract Transforming growth factor beta-1 (TGF-β1) plays a key role in Cardiovascular disease by a process which allows the loss of its protective properties. The first therapeutic attempt to restore its function by selectively designed novel drugs are being made. In addition, it has been recognized that the TGF-β1 pathway is involved in the vascular mechanism of action of some current clinical drugs, such as acetylsalicylic acid, thiazolidinediones and statins. The aim of this paper is to review the possible value of TGF-β1 as both a disease marker and a therapeutical target for Cardiovascular disease.
Tilo Grosser - One of the best experts on this subject based on the ideXlab platform.
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The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs.
Trends in pharmacological sciences, 2017Co-Authors: Tilo Grosser, Emanuela Ricciotti, Garret A. FitzgeraldAbstract:The principal molecular mechanisms underlying the Cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and their relative predisposition to complications. In review article, we discuss how heterogeneity in the pharmacokinetics and pharmacodynamics of distinct NSAIDs may be expected to affect their CV risk profile. We consider evidence afforded by studies in model systems, mechanistic clinical trials, a meta-analysis of randomized controlled trials, and two recent large clinical trials, Standard Care vs. Celecoxib Outcome Trial (SCOT) and Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION), designed specifically to compare the CV safety of the cyclooxygenase-2-selective NSAID, celecoxib, with traditional NSAIDs. We conclude that SCOT and PRECISION have apparently not compared equipotent doses and have other limitations that bias them toward underestimation of the relative risk of celecoxib.
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The Cardiovascular Pharmacology of COX-2 Inhibition
Hematology. American Society of Hematology. Education Program, 2005Co-Authors: Susanne Fries, Tilo GrosserAbstract:Selective inhibitors of cyclooxygenase (COX)-2, the coxibs, were developed to inhibit inflammatory prostaglandins derived from COX-2, while sparing gastroprotective prostaglandins primarily formed by COX-1. However, COX-2-derived prostaglandins mediate not only pain and inflammation but also affect vascular function, the regulation of hemostasis/ thrombosis, and blood pressure control. All coxibs depress COX-2-dependent prostacyclin (PGI(2)) biosynthesis without effective suppression of platelet COX-1-derived thromboxane (Tx) A(2), unlike aspirin or traditional nonsteroidal anti-inflammatory drugs, which inhibit both COX-1 and COX-2. The actions of PGI(2) oppose mediators, which stimulate platelets, elevate blood pressure, and accelerate atherogenesis, including TxA(2). Indeed, structurally distinct inhibitors of COX-2 have increased the likelihood of hypertension, myocardial infarction and stroke in controlled clinical trials. The detection of these events in patients is related to the duration of exposure and to their baseline risk of Cardiovascular disease. Thus, coxibs should be withheld from patients with preexisting Cardiovascular risk factors, and exposed patients at low Cardiovascular baseline risk should be monitored for changes in their risk factor profile, such as increases in arterial blood pressure.
Santiago Redondo - One of the best experts on this subject based on the ideXlab platform.
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TGF-beta1: a novel target for Cardiovascular Pharmacology.
Cytokine & growth factor reviews, 2007Co-Authors: Santiago Redondo, Carlos G Santos-gallego, Teresa TejerinaAbstract:Transforming growth factor beta-1 (TGF-beta1) plays a key role in Cardiovascular disease by a process which allows the loss of its protective properties. The first therapeutic attempt to restore its function by selectively designed novel drugs are being made. In addition, it has been recognized that the TGF-beta1 pathway is involved in the vascular mechanism of action of some current clinical drugs, such as acetylsalicylic acid, thiazolidinediones and statins. The aim of this paper is to review the possible value of TGF-beta1 as both a disease marker and a therapeutical target for Cardiovascular disease.
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TGF-β1: a novel target for Cardiovascular Pharmacology
Cytokine & Growth Factor Reviews, 2007Co-Authors: Santiago Redondo, Carlos G Santos-gallego, Teresa TejerinaAbstract:Abstract Transforming growth factor beta-1 (TGF-β1) plays a key role in Cardiovascular disease by a process which allows the loss of its protective properties. The first therapeutic attempt to restore its function by selectively designed novel drugs are being made. In addition, it has been recognized that the TGF-β1 pathway is involved in the vascular mechanism of action of some current clinical drugs, such as acetylsalicylic acid, thiazolidinediones and statins. The aim of this paper is to review the possible value of TGF-β1 as both a disease marker and a therapeutical target for Cardiovascular disease.