Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque dest...Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.展开更多
Inflammation plays an important role in atherosclerosis.Inflammasomes play a crucial role in innate immunity,which mediates the body’s response to various pathogens.Of the different types of inflammasomes,NLRP3 has b...Inflammation plays an important role in atherosclerosis.Inflammasomes play a crucial role in innate immunity,which mediates the body’s response to various pathogens.Of the different types of inflammasomes,NLRP3 has been implicated in atherosclerosis through the production of proinfl ammatory cytokines,IL-1β and IL-18.This review describes the role of the NLRP3 infl ammasome in atherosclerosis and discusses potential therapeutic targets in the infl ammasome pathway.展开更多
After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus(HIV) in developed countries has increased substantially. This has allowe...After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus(HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease(CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial.展开更多
基金Supported by FORICA(the FOundation for Advanced Research in Hypertension and Cardiovascular diseases,www.forica.it)
文摘Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.
文摘Inflammation plays an important role in atherosclerosis.Inflammasomes play a crucial role in innate immunity,which mediates the body’s response to various pathogens.Of the different types of inflammasomes,NLRP3 has been implicated in atherosclerosis through the production of proinfl ammatory cytokines,IL-1β and IL-18.This review describes the role of the NLRP3 infl ammasome in atherosclerosis and discusses potential therapeutic targets in the infl ammasome pathway.
文摘After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus(HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease(CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial.
