Sha Li, R. Xu, Yuan-Lin Guo, Yan Zhang, Cheng-gang Zhu, Jing Sun, Jian‐Jun Li
Abstract Thyroid function and PCSK9 in euthyroid subjects with coronary artery disease Background: Both thyroid hormone and PCSK9 are key regulators of lipid metabolism. Their respective impacts on dylipidemia and the development of associated coronary artery disease (CAD) have received continued interest. Aim: To examine whether plasma PCSK9 levels were correlated with thyroid hormones in euthyroid subjects with stable CAD. Materials & methods: A total of 447 euthyroid subjects with stable CAD were prospectively enrolled. Angiography and lipid-lowering therapy were parts of the screening process. Baseline clinical characteristics were collected. Fasting free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), glucose and lipid profiles were measured. Plasma PCSK9 levels were determined by ELISA. Results: Plasma PCSK9 levels exhibited an inverse correlation with FT3 (r = -0.182, p < 0.001) and a positive correlation with TSH (r = -0.100, p = 0.035). After adjustment for cardiometabolic risk factors, patients with higher levels of PCSK9 differed from those with lower levels of PCSK9 in FT3, FT4 and TSH levels (p < 0.05, all). When Logistic analysis was performed with PCSK9 tertiles as the dependent variable, FT3 (OR = 0.430, 95% CI: 0.206–0.897), FT4 (OR = 0.863, 95% CI: 0.708–0.995) and TSH (OR = 2.114, 95% CI: 1.003–4.457) exhibited independent associations with an elevated PCSK9 level (tertile 3). Finally, multiple linear analysis revealed that PCSK9 levels were related significantly and independently to FT3 (β = -0.110, p = 0.019) but not FT4 (β = -0.073, p = 0.110) or TSH (β = -0.087, p = 0.060). Conclusion: The study demonstrates a negative association between thyroid function and PCSK9 levels in euthyroid subjects with stable CAD, suggesting a potential interaction between PCSK9 and lower levels of thyroid hormones in patients with CAD.
{"title":"Thyroid function and PCSK9 in euthyroid subjects with coronary artery disease","authors":"Sha Li, R. Xu, Yuan-Lin Guo, Yan Zhang, Cheng-gang Zhu, Jing Sun, Jian‐Jun Li","doi":"10.2217/clp.15.13","DOIUrl":"https://doi.org/10.2217/clp.15.13","url":null,"abstract":"Abstract Thyroid function and PCSK9 in euthyroid subjects with coronary artery disease Background: Both thyroid hormone and PCSK9 are key regulators of lipid metabolism. Their respective impacts on dylipidemia and the development of associated coronary artery disease (CAD) have received continued interest. Aim: To examine whether plasma PCSK9 levels were correlated with thyroid hormones in euthyroid subjects with stable CAD. Materials & methods: A total of 447 euthyroid subjects with stable CAD were prospectively enrolled. Angiography and lipid-lowering therapy were parts of the screening process. Baseline clinical characteristics were collected. Fasting free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), glucose and lipid profiles were measured. Plasma PCSK9 levels were determined by ELISA. Results: Plasma PCSK9 levels exhibited an inverse correlation with FT3 (r = -0.182, p < 0.001) and a positive correlation with TSH (r = -0.100, p = 0.035). After adjustment for cardiometabolic risk factors, patients with higher levels of PCSK9 differed from those with lower levels of PCSK9 in FT3, FT4 and TSH levels (p < 0.05, all). When Logistic analysis was performed with PCSK9 tertiles as the dependent variable, FT3 (OR = 0.430, 95% CI: 0.206–0.897), FT4 (OR = 0.863, 95% CI: 0.708–0.995) and TSH (OR = 2.114, 95% CI: 1.003–4.457) exhibited independent associations with an elevated PCSK9 level (tertile 3). Finally, multiple linear analysis revealed that PCSK9 levels were related significantly and independently to FT3 (β = -0.110, p = 0.019) but not FT4 (β = -0.073, p = 0.110) or TSH (β = -0.087, p = 0.060). Conclusion: The study demonstrates a negative association between thyroid function and PCSK9 levels in euthyroid subjects with stable CAD, suggesting a potential interaction between PCSK9 and lower levels of thyroid hormones in patients with CAD.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"30 1","pages":"235 - 242"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81192446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Rinkūnienė, A. Laucevičius, Ž. Petrulionienė, V. Dženkevičiūtė, S. Kutkiene, Agnė Skujaitė, V. Kasiulevičius
Abstract Aim: The aim of this study was to assess the prevalence of dyslipidemia and its relation to other cardiovascular risk factors in Lithuania. Design & methods: The Lithuanian High Cardiovascular Risk Primary Prevention program recruited men and women without overt cardiovascular disease. This report describes the group of 23,204 subjects. Results: Dyslipidemia was diagnosed in 89.7% of subjects. All the main cardiovascular risk factors except for smoking were present more often among patients with dyslipidemia. The average number of risk factors (arterial hypertension, abdominal obesity, diabetes mellitus, metabolic syndrome, smoking, insufficient physical activity, unbalanced diet and family history of CVD) in subjects with dyslipidemia was 3.09 (compared with 2.42 in subjects without it). Conclusion: Dyslipidemia is a most frequent risk factor among middle-aged Lithuanian subjects without cardiovascular disease and has been diagnosed in nine out of ten subjects.
{"title":"The prevalence of dislipidemia and its relation to other risk factors: a nationwide survey of Lithuania","authors":"E. Rinkūnienė, A. Laucevičius, Ž. Petrulionienė, V. Dženkevičiūtė, S. Kutkiene, Agnė Skujaitė, V. Kasiulevičius","doi":"10.2217/clp.15.16","DOIUrl":"https://doi.org/10.2217/clp.15.16","url":null,"abstract":"Abstract Aim: The aim of this study was to assess the prevalence of dyslipidemia and its relation to other cardiovascular risk factors in Lithuania. Design & methods: The Lithuanian High Cardiovascular Risk Primary Prevention program recruited men and women without overt cardiovascular disease. This report describes the group of 23,204 subjects. Results: Dyslipidemia was diagnosed in 89.7% of subjects. All the main cardiovascular risk factors except for smoking were present more often among patients with dyslipidemia. The average number of risk factors (arterial hypertension, abdominal obesity, diabetes mellitus, metabolic syndrome, smoking, insufficient physical activity, unbalanced diet and family history of CVD) in subjects with dyslipidemia was 3.09 (compared with 2.42 in subjects without it). Conclusion: Dyslipidemia is a most frequent risk factor among middle-aged Lithuanian subjects without cardiovascular disease and has been diagnosed in nine out of ten subjects.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"27 1","pages":"219 - 225"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78731057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Polycystic ovarian syndrome is a common endocrine disorder of women. It is associated with an adverse metabolic risk factor profile including hyperinsulinemia, abnormal glucose metabolism, dyslipidemia and chronic pro-atherogenic low grade inflammation. A large proportion of PCOS women are overweight or obese; these women have a high prevalence of insulin resistance and some studies suggest this also the case in lean women with PCOS. Impaired glucose tolerance and diabetes are more common in women with PCOS than in the general population. Besides conventional atherogenic dyslipidemia, PCOS women have additional abnormalities including elevations in small, dense LDL and dysfunctional HDL-particles. Despite a clear pro-atherogenic risk factor profile, it has not been clearly demonstrated that this translates into increased cardiovascular morbidity and mortality in this population.
{"title":"Metabolic and lipoprotein aspects of polycystic ovarian syndrome","authors":"A. Pazderska, J. Gibney","doi":"10.2217/clp.15.12","DOIUrl":"https://doi.org/10.2217/clp.15.12","url":null,"abstract":"Abstract Polycystic ovarian syndrome is a common endocrine disorder of women. It is associated with an adverse metabolic risk factor profile including hyperinsulinemia, abnormal glucose metabolism, dyslipidemia and chronic pro-atherogenic low grade inflammation. A large proportion of PCOS women are overweight or obese; these women have a high prevalence of insulin resistance and some studies suggest this also the case in lean women with PCOS. Impaired glucose tolerance and diabetes are more common in women with PCOS than in the general population. Besides conventional atherogenic dyslipidemia, PCOS women have additional abnormalities including elevations in small, dense LDL and dysfunctional HDL-particles. Despite a clear pro-atherogenic risk factor profile, it has not been clearly demonstrated that this translates into increased cardiovascular morbidity and mortality in this population.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"7 1","pages":"281 - 293"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82892038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Stanimirovic, M. Obradović, S. Zafirovic, I. Resanović, Nikola Bogdanović, Z. Gluvić, S. Mousa, E. Isenovic
Abstract An altered hepatic lipid metabolism involves multifactorial pathologies such as hepatic inflammation, insulin resistance and oxidative stress. Immunity has an essential role in the regulation of glucose and lipid metabolism in the liver. Inducible nitric oxide (NO) synthase (iNOS) has been proposed as an important factor that interplays between immunity and energy metabolism and also in the pathogenesis of obesity-linked insulin resistance. In the liver, locally produced NO plays a protective role during inflammation, and the balance of NO protective and cytotoxic effects is very important. This review is focused on understanding the molecular mechanisms of iNOS regulation in the state of altered hepatic lipid metabolism, which is critical for developing new strategies for treatment of hepatic disorders.
{"title":"Effects of altered hepatic lipid metabolism on regulation of hepatic iNOS","authors":"J. Stanimirovic, M. Obradović, S. Zafirovic, I. Resanović, Nikola Bogdanović, Z. Gluvić, S. Mousa, E. Isenovic","doi":"10.2217/clp.15.8","DOIUrl":"https://doi.org/10.2217/clp.15.8","url":null,"abstract":"Abstract An altered hepatic lipid metabolism involves multifactorial pathologies such as hepatic inflammation, insulin resistance and oxidative stress. Immunity has an essential role in the regulation of glucose and lipid metabolism in the liver. Inducible nitric oxide (NO) synthase (iNOS) has been proposed as an important factor that interplays between immunity and energy metabolism and also in the pathogenesis of obesity-linked insulin resistance. In the liver, locally produced NO plays a protective role during inflammation, and the balance of NO protective and cytotoxic effects is very important. This review is focused on understanding the molecular mechanisms of iNOS regulation in the state of altered hepatic lipid metabolism, which is critical for developing new strategies for treatment of hepatic disorders.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"50 1","pages":"167 - 175"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87030859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Arthur, A. Rodríguez-Vida, G. Zadra, H. Møller, M. Hemelrijck
Abstract With the current epidemic of lipid-related disorders and prostate cancer (PCa) in western countries, there is growing interest in the potential causal relationship between lipids and PCa. PCa is a heterogeneous disease, which undermines researchers’ ability to determine the mechanistic pathways responsible for its development and progression. Currently, detection and progression of PCa is mainly determined by prostate specific antigen, but this biomarker lacks specificity and is unable to discriminate between indolent and aggressive cancer. Nonetheless, there is evidence to suggest that lipid markers might potentially be useful in conjunction with other markers such as prostate specific antigen in improving detection and management of this disease. This review aims to highlight findings from epidemiological studies which examined the role of serum lipids in PCa occurrence and prognosis.
{"title":"Serum lipids as markers of prostate cancer occurrence and prognosis?","authors":"R. Arthur, A. Rodríguez-Vida, G. Zadra, H. Møller, M. Hemelrijck","doi":"10.2217/clp.14.69","DOIUrl":"https://doi.org/10.2217/clp.14.69","url":null,"abstract":"Abstract With the current epidemic of lipid-related disorders and prostate cancer (PCa) in western countries, there is growing interest in the potential causal relationship between lipids and PCa. PCa is a heterogeneous disease, which undermines researchers’ ability to determine the mechanistic pathways responsible for its development and progression. Currently, detection and progression of PCa is mainly determined by prostate specific antigen, but this biomarker lacks specificity and is unable to discriminate between indolent and aggressive cancer. Nonetheless, there is evidence to suggest that lipid markers might potentially be useful in conjunction with other markers such as prostate specific antigen in improving detection and management of this disease. This review aims to highlight findings from epidemiological studies which examined the role of serum lipids in PCa occurrence and prognosis.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"98 1","pages":"145 - 165"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81163010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract “The current evidence indicates that the polyunsaturated fatty acids have cardioprotective benefits and that both n-3 and n-6 polyunsaturated fatty acids are beneficial.”
{"title":"Dietary polyunsaturated fat intake in coronary heart disease risk","authors":"J. Virtanen","doi":"10.2217/clp.15.5","DOIUrl":"https://doi.org/10.2217/clp.15.5","url":null,"abstract":"Abstract “The current evidence indicates that the polyunsaturated fatty acids have cardioprotective benefits and that both n-3 and n-6 polyunsaturated fatty acids are beneficial.”","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"43 1","pages":"115 - 117"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82092674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Hypertriglyceridemia is a common feature of many metabolic disorders and has been identified as risk factor for cardiovascular disease. ApoC-III is commonly associated with triglyceride rich lipoproteins and has been identified as a potent modulator of plasma TG levels. The purpose of this review is to provide background on apoC-III and its role in the regulation of plasma TG and lipoprotein metabolism and to highlight preclinical and genetic evidence supporting apoC-III as a central target in cardiovascular disease progression. Finally, recent results from clinical trials evaluating a second generation antisense oligonucleotide (ASO) inhibitor of apoC-III will be summarized and the potential impact such a drug could have in the treatment of hypertriglyceridemia and associated comorbidities will be highlighted.
{"title":"Therapeutic inhibition of apoC-III for the treatment of hypertriglyceridemia","authors":"T. Bell, M. Graham, B. Baker, R. Crooke","doi":"10.2217/clp.15.7","DOIUrl":"https://doi.org/10.2217/clp.15.7","url":null,"abstract":"Abstract Hypertriglyceridemia is a common feature of many metabolic disorders and has been identified as risk factor for cardiovascular disease. ApoC-III is commonly associated with triglyceride rich lipoproteins and has been identified as a potent modulator of plasma TG levels. The purpose of this review is to provide background on apoC-III and its role in the regulation of plasma TG and lipoprotein metabolism and to highlight preclinical and genetic evidence supporting apoC-III as a central target in cardiovascular disease progression. Finally, recent results from clinical trials evaluating a second generation antisense oligonucleotide (ASO) inhibitor of apoC-III will be summarized and the potential impact such a drug could have in the treatment of hypertriglyceridemia and associated comorbidities will be highlighted.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"35 1","pages":"191 - 203"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87154977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Aims: ApoB and non-HDL-C more accurately quantify cardiovascular risk than LDL-C; however, controversies exist over which is more clinically useful. We determined how well non-HDL-C targets predicted the attainment of apoB goals. Materials & Methods: In this cross-sectional study of Type 2 diabetic patients who achieved LDL-C <100 mg/dl, apoB and non-HDL-C concentrations, and the accuracy of non-HDL-C targets against apoB goals were determined. Results: Positive predictive values of non-HDL-C goals in predicting attainment of apoB goals were 90.3%, but were reduced in patients with hypertriglyceridemia or coronary heart disease (CHD). Conclusion: ApoB measurement could be useful in evaluating cardiovascular risk in diabetic subjects with hypertriglyceridemia or CHD who have already achieved LDL-C and non-HDL-C targets.
{"title":"The role of apoB measurement in Type 2 diabetic patients","authors":"Brian Lee, Busadee Pratumvinit, N. Thongtang","doi":"10.2217/clp.15.6","DOIUrl":"https://doi.org/10.2217/clp.15.6","url":null,"abstract":"Abstract Aims: ApoB and non-HDL-C more accurately quantify cardiovascular risk than LDL-C; however, controversies exist over which is more clinically useful. We determined how well non-HDL-C targets predicted the attainment of apoB goals. Materials & Methods: In this cross-sectional study of Type 2 diabetic patients who achieved LDL-C <100 mg/dl, apoB and non-HDL-C concentrations, and the accuracy of non-HDL-C targets against apoB goals were determined. Results: Positive predictive values of non-HDL-C goals in predicting attainment of apoB goals were 90.3%, but were reduced in patients with hypertriglyceridemia or coronary heart disease (CHD). Conclusion: ApoB measurement could be useful in evaluating cardiovascular risk in diabetic subjects with hypertriglyceridemia or CHD who have already achieved LDL-C and non-HDL-C targets.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"62 1","pages":"137 - 144"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80912897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Ninić, V. Spasojević-Kalimanovska, N. Bogavac-Stanojević, J. Kotur-Stevuljević, Danijela Kornic-Ristovski, A. Stefanović, S. Spasić, M. Deanović, S. Babka, B. Aleksic, Z. Jelić-Ivanović
Abstract Aim: The purpose of this study was to investigate the relationship between anthropometric parameters and serum lipid concentrations in both preadolescent and adolescent girls and boys. Materials & Methods: Basic lipid status parameters were determined in fasting venous blood from 186 preadolescents and adolescents. Atherogenic indices were calculated. Results: Two-way analysis of variance showed significant interactions between age and BMI subgroups in girls at the level of HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C, total cholesterol/HDL-C and LDL-C/HDL-C. Ordinal regression analysis showed that increasing age in both genders reduced the probability of higher HDL-C concentrations. Conclusion: Age was an independent predictor for lower HDL-C concentration in both genders. BMI was the most significant independent predictor for most lipid parameters in girls.
{"title":"Associations between anthropometric parameters and serum lipids in preadolescent and adolescent girls and boys","authors":"A. Ninić, V. Spasojević-Kalimanovska, N. Bogavac-Stanojević, J. Kotur-Stevuljević, Danijela Kornic-Ristovski, A. Stefanović, S. Spasić, M. Deanović, S. Babka, B. Aleksic, Z. Jelić-Ivanović","doi":"10.2217/clp.15.2","DOIUrl":"https://doi.org/10.2217/clp.15.2","url":null,"abstract":"Abstract Aim: The purpose of this study was to investigate the relationship between anthropometric parameters and serum lipid concentrations in both preadolescent and adolescent girls and boys. Materials & Methods: Basic lipid status parameters were determined in fasting venous blood from 186 preadolescents and adolescents. Atherogenic indices were calculated. Results: Two-way analysis of variance showed significant interactions between age and BMI subgroups in girls at the level of HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C, total cholesterol/HDL-C and LDL-C/HDL-C. Ordinal regression analysis showed that increasing age in both genders reduced the probability of higher HDL-C concentrations. Conclusion: Age was an independent predictor for lower HDL-C concentration in both genders. BMI was the most significant independent predictor for most lipid parameters in girls.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"3 1","pages":"119 - 128"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81580057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract The discovery that lysophosphatidic acid (LPA) acts as a signaling molecule via its G protein-coupled receptors motivated studies on the signaling and pathophysiology of LPA. Furthermore, the subsequent identification of the LPA-producing plasma phosphodiesterase, autotaxin, led to structural and mouse genetic studies of this lysophospholipase D. Recently, translational studies using LPA receptor-deficient or autotaxin-deficient mice, as well as receptor specific antagonists and autotaxin inhibitors, have been reported. These reports suggest that autotaxin and LPA receptors are potential drug targets, and have attracted the attention of researchers involved in drug discovery in a variety of pathologies including cancer, fibrosis, inflammation, pain and cardiovascular diseases. In this review, the state of the art regarding translational research and the status of drug discovery efforts targeting LPA synthesis (autotaxin) and LPA signaling (LPA receptors) are discussed with an emphasis on potential clinical applications.
{"title":"Translational research on autotaxin-LPA-LPA receptors and drug discovery","authors":"D. Im","doi":"10.2217/clp.15.4","DOIUrl":"https://doi.org/10.2217/clp.15.4","url":null,"abstract":"Abstract The discovery that lysophosphatidic acid (LPA) acts as a signaling molecule via its G protein-coupled receptors motivated studies on the signaling and pathophysiology of LPA. Furthermore, the subsequent identification of the LPA-producing plasma phosphodiesterase, autotaxin, led to structural and mouse genetic studies of this lysophospholipase D. Recently, translational studies using LPA receptor-deficient or autotaxin-deficient mice, as well as receptor specific antagonists and autotaxin inhibitors, have been reported. These reports suggest that autotaxin and LPA receptors are potential drug targets, and have attracted the attention of researchers involved in drug discovery in a variety of pathologies including cancer, fibrosis, inflammation, pain and cardiovascular diseases. In this review, the state of the art regarding translational research and the status of drug discovery efforts targeting LPA synthesis (autotaxin) and LPA signaling (LPA receptors) are discussed with an emphasis on potential clinical applications.","PeriodicalId":55252,"journal":{"name":"Clinical Lipidology","volume":"34 1","pages":"177 - 190"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78432640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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