Article
Cardiac & Cardiovascular Systems
Kei Sasaki, Hayato Tada, Masa-aki Kawashiri, Toshimitsu Ito
Summary: We report a highly rare family where the phenotypes of familial hypercholesterolemia are canceled out by the coexistence of type 1 familial hypobetalipoproteinemia caused by an APOB truncating mutation.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Elena Grao-Cruces, Carmen M. Claro-Cala, Sergio Montserrat de la Paz, Clevio Nobrega
Summary: Alzheimer's disease (AD), characterized by amyloid plaques and tau neurofibrillary tangles, is the most common form of dementia. Neuroinflammation and cellular stress have emerged as important factors in AD development and pathology. Chronic stress leads to the formation of stress granules (SGs), which have a protective role but can become pathological and neurotoxic, contributing to increased tau aggregation. Impaired lipid metabolism, specifically cholesterol efflux and lipid transport, is associated with a higher risk of AD. This review provides insight into the interplay between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Luis Filipe Teixeira da Costa
Summary: The investigation of familial hypercholesterolemia (FH) and its relationship to atherosclerosis has led to significant scientific and medical progress. Understanding genetic defects, molecular mechanisms, and pharmaceutical tools for FH treatment has shifted the focus to cellular processes and highlighted the role of LDL uptake deficiency. However, whole organism fluxes of cholesterol are liver-centered and evolutionary pressures favor mechanisms maintaining LDL plasma concentrations. The findings suggest a signaling defect in liver rather than an uptake deficiency as the fundamental cause of hypercholesterolemia.
MEDICAL HYPOTHESES
(2021)
Review
Pathology
Chiara Macchi, Nicola Ferri, Cesare R. Sirtori, Alberto Corsini, Maciej Banach, Massimiliano Ruscica
Summary: PCSK9, mainly synthesized and released by the liver, is a key regulator of low-density lipoprotein cholesterol, with potential non-cholesterol-related effects in inflammatory burden, triglyceride-rich lipoprotein metabolism, platelet activation, and possibly in diseases such as diabetes, obesity, and cancer. Further research is needed to understand the diverse roles of PCSK9 in various physiological and pathological processes.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Victoria Marco-Benedi, Ana Cenarro, Martin Laclaustra, Asier Larrea-Sebal, Estibaliz Jarauta, Itziar Lamiquiz-Moneo, Pilar Calmarza, Ana M. Bea, Nuria Plana, Xavier Pinto, Cesar Martin, Fernando Civeira
Summary: This study aimed to compare Lp(a) concentration in controls, genetically diagnosed heFH, and mutation-negative hypercholesterolemia subjects, as well as to assess the influence of the genetic defect responsible for heFH on Lp(a) concentration. The results showed that Lp(a) concentration was elevated in mutation-negative subjects and heFH patients. Among heFH patients, APOB-dependent FH had the highest Lp(a) concentration, followed by LDLR-dependent FH.
Article
Biochemistry & Molecular Biology
Jacek Jasiecki, Monika Targonska, Anna Janaszak-Jasiecka, Magdalena Chmara, Monika Zuk, Leszek Kalinowski, Krzysztof Waleron, Bartosz Wasag
Summary: Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the LDL receptor (LDLR) gene, leading to an increased risk of cardiovascular diseases. This study developed a single-cell, kinetic, fluorescent LDL uptake assay to analyze the function of LDLR gene variants. It also established a human cell line with LDLR deficiency and a reporter system for studying LDLR gene transcriptional regulation, which can aid in drug testing for atherosclerosis therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Julia Brandts, Kausik K. Ray
Summary: Early detection of FH and normalization of LDL cholesterol levels are crucial for preventing cardiovascular disease. Various treatments targeting LDL receptor-dependent and independent pathways can be used to manage FH effectively.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Maggie Wang, Adekunle Alabi, Hong-mei Gu, Govind Gill, Ziyang Zhang, Suha Jarad, Xiao-dan Xia, Yishi Shen, Gui-qing Wang, Da-wei Zhang
Summary: This study investigates the determinants of MT1-MMP-induced LDLR cleavage in LDLR and MT1-MMP. The study finds that MT1-MMP does not require a specific cleavage site on LDLR, but an amino acid residue with a hydrophobic side chain at position 167 in the MT-loop is critical for MT1-MMP-induced LDLR cleavage.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biology
Jui-Tung Liu, Caren Doueiry, Yu-lin Jiang, Josef Blaszkiewicz, Mary Paige Lamprecht, James A. A. Heslop, Yuri K. K. Peterson, Juliana Debrito Carten, Paula Traktman, Yang Yuan, Salman R. R. Khetani, Waleed O. O. Twal, Stephen A. A. Duncan
Summary: iPSC-derived hepatocytes were used to identify small molecule inhibitors of apoB secretion without causing steatosis. These inhibitors show effectiveness in reducing apoB secretion in cultured hepatocytes and humanized livers in mice. This research provides a potential solution for treating FH patients with hoFH mutations, with the identified small molecules having a distinct chemical structure from existing cholesterol lowering drugs.
COMMUNICATIONS BIOLOGY
(2023)
Article
Nutrition & Dietetics
Hongen Meng, Li Jiang, Zijun Song, Fudi Wang
Summary: This study used Mendelian randomization to evaluate the genetic causal effects of circulating apolipoproteins and lipoprotein lipids on osteoarthritis (OA) risk. The results showed that genetic predisposition to Apolipoprotein B (APOB) and low-density lipoprotein (LDL) was associated with a decreased risk of OA, providing new insights into the relationship between lipids and OA risk.
Article
Nutrition & Dietetics
Rihwa Choi, Sang Gon Lee, Eun Hee Lee
Summary: This study investigated the prevalence of sdLDL predominant phenotype in Korean adult patients and found that a significant proportion of patients had increased risk only due to sdLDL. This suggests that LDL particle size analysis has clinical significance in the Korean population.
Article
Biochemistry & Molecular Biology
Yuanyu Huang, Shuquan Zheng, Zhaoxu Guo, Xavier de Mollerat du Jeu, Xing-Jie Liang, Zhiwei Yang, Hong-Yan Zhang, Shan Gao, Zicai Liang
Summary: This study developed a novel nanoparticle and lyophilization technology for the effective delivery of siRNA into hepatocytes for hepatitis B treatment. The results showed that this therapeutic approach significantly suppressed viral replication and antigen expression, in contrast to the limited impact of current clinically-employed drugs.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Bingxiang Wang, Yishi Shen, Lei Zhai, Xiaodan Xia, Hong-mei Gu, Maggie Wang, Yongfang Zhao, Xiaole Chang, Adekunle Alabi, Sijie Xing, Shijun Deng, Boyan Liu, Guiqing Wang, Shucun Qin, Da-wei Zhang
Summary: Deficiency of Surf4 in the liver reduces secretion of VLDL and the development of atherosclerosis without causing significant hepatic lipid accumulation or liver damage.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kevin Chemello, Javier Garcia-Nafria, Antonio Gallo, Cesar Martin, Gilles Lambert, Dirk Blom
Summary: Familial hypercholesterolemia is a common genetic disorder characterized by high levels of LDL-C and increased risk of premature cardiovascular events. Research focuses on clinical phenotypes, genetic variants, and therapeutic approaches.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Shirin Ibrahim, Jeroen van Rooij, Annemieke J. M. H. Verkerk, Jard de Vries, Linda Zuurbier, Joep Defesche, Jorge Peter, Willemijn A. M. Schonck, Bahar Sedaghati-Khayat, G. Kees Hovingh, Andre G. Uitterlinden, Erik S. G. Stroes, Laurens F. Reeskamp
Summary: This study evaluated the accuracy of a low-cost, high-throughput genotyping array for diagnosing familial hypercholesterolemia (FH). The results showed that the array had a high coverage and sensitivity for FH-causing variants, and could identify additional FH-causing variants. The array has the potential to increase accessibility to genetic testing for FH at a low cost.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Gerald F. Watts, David R. Sullivan, David L. Hare, Karam M. Kostner, Ari E. Horton, Damon A. Bell, Tom Brett, Ronald J. Trent, Nicola K. Poplawski, Andrew C. Martin, Shubha Srinivasan, Robert N. Justo, Clara K. Chow, Jing Pang
Summary: Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder that leads to cardiovascular diseases. Despite approximately 100,000 affected individuals in Australia, the majority remain undetected and untreated. Updated guidance has been provided to address the care of patients and families with FH, emphasizing the importance of detection, diagnosis, assessment, management, genetic testing, risk notification, and adherence to heart-healthy lifestyles.
HEART LUNG AND CIRCULATION
(2021)
Review
Endocrinology & Metabolism
Nick S. R. Lan, Kharis Burns, Damon A. Bell, Gerald F. Watts
Summary: Dyslipidaemia is a major modifiable risk factor for ASCVD in type 2 diabetes patients. Recent trials have shown that ezetimibe and PCSK9 inhibitors are more beneficial for diabetes patients. International guidelines now recommend a more intensive approach to treating dyslipidaemia in diabetes patients.
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2021)
Article
Cardiac & Cardiovascular Systems
Nick S. R. Lan, Dick C. Chan, Jing Pang, P. Gerry Fegan, Bu B. Yeap, James M. Rankin, Carl J. Schultz, Gerald F. Watts, Damon A. Bell
Summary: Lipoprotein(a) and diabetes are both independently associated with premature coronary artery disease (pCAD), but there is a negative relationship between Lp(a) concentration and the risk of type 2 diabetes (T2D). This study found that in coronary care patients with pCAD, those with T2D had lower Lp(a) concentrations, but elevated Lp(a) was still predictive of pCAD in patients with T2D.
HEART LUNG AND CIRCULATION
(2021)
Letter
Cardiac & Cardiovascular Systems
Nick S. R. Lan, Girish Dwivedi, Damon A. Bell
HEART LUNG AND CIRCULATION
(2021)
Article
Pediatrics
Andrew C. Martin, Amanda J. Hooper, Richard Norman, Lan T. Nguyen, John R. Burnett, Damon A. Bell, Tom Brett, Jacquie Garton-Smith, Jing Pang, Kristen J. Nowak, Gerald F. Watts
Summary: Universal screening of children aged 1-2 years for FH during immunisations was proven to be feasible, effective, and cost-effective in detecting FH cases among children, parents, and other relatives.
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Article
Cardiac & Cardiovascular Systems
Anindita Chakraborty, Jing Pang, Dick C. Chan, Katrina L. Ellis, Amanda J. Hooper, Damon A. Bell, John R. Burnett, Eric K. Moses, Gerald F. Watts
Summary: This study investigated the detection of new cases of elevated Lp(a) during cascade testing of relatives of probands with a definite diagnosis of FH and elevated Lp(a). The findings suggest that a dual approach to cascade testing families for FH and high Lp(a) from appropriate probands can effectively identify new cases of FH and elevated Lp(a).
Letter
Cardiac & Cardiovascular Systems
Russell S. Wong, Nick S. R. Lan, James M. Rankin, Damon A. Bell, Girish Dwivedi
CORONARY ARTERY DISEASE
(2022)
Article
Cardiac & Cardiovascular Systems
Robert Larbalestier, Girish Dwivedi, Nick S. R. Lan, Umar S. Ali, Damon A. Bell
Summary: A retrospective analysis was conducted to determine the potential eligibility of coronary artery bypass graft (CABG) surgery patients for icosapent ethyl therapy. The study found that a substantial percentage of these patients may be eligible for the therapy and could potentially benefit from its cardiovascular protection. Further research should evaluate the additional cardiovascular benefits of icosapent ethyl in this high-risk group of patients who are already treated with high-intensity statins.
CARDIOVASCULAR REVASCULARIZATION MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Michael M. Page, Katrina L. Ellis, Dick C. Chan, Jing Pang, Amanda J. Hooper, Damon A. Bell, John R. Burnett, Eric K. Moses, Gerald F. Watts
Summary: The rs1250229-T allele of the FN1 gene is inversely associated with CAD in patients with genetically confirmed FH, independently of traditional risk factors. This finding suggests that the biology of fibronectin may contribute to the variation in CAD risk in FH patients.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Review
Endocrinology & Metabolism
Nick S. R. Lan, Damon A. Bell, Gerald F. Watts, P. Gerry Fegan
Summary: This article discusses the recommendations for lipid-lowering therapy, management of hypertriglyceridemia, and potential barriers to optimal care in adults with type 1 diabetes (T1D). Low-density lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering, but international guidelines have differing approaches to ASCVD risk-stratification, lipid-lowering, and LDL-C goals in individuals with diabetes.
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2023)
Article
Pathology
Nicola Sawyer, Paul Glendenning, Samuel D. Vasikaran, Michael M. Page, Sze Ling Wong, Jun Yang, Markus P. Schlaich, Greg Van Schie, Damon A. Bell
Summary: The objective of this study was to determine the clinical and biochemical success rates of adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS), using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were evaluated retrospectively in patients who underwent adrenalectomy according to AVS between September 2017 and September 2020. Follow-up data were collected through questionnaires, clinic letter reviews, and examination of pathology and radiological reports. The results showed high clinical and biochemical success rates in patients who underwent adrenalectomy for unilateral PA in Western Australia, but further standardization of post-operative follow-up care is needed.
Meeting Abstract
Dermatology
Aaron Frederiks, Sujith Prasad Kumarasinghe, Damon Bell
AUSTRALASIAN JOURNAL OF DERMATOLOGY
(2022)
Article
Endocrinology & Metabolism
Elaine E. Sanderson, Mark Shah, Amanda J. Hooper, Damon A. Bell, Catherine S. Choong
Summary: This case report highlights a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene in an 11-year-old girl. It emphasizes the importance of genetic evaluation in atypical presentations of diabetes in children and adolescents, as INSR gene variants can be a cause of monogenic diabetes. The article also discusses the potential role of metformin in treating type A insulin resistance syndrome due to INSR gene variants.
ENDOCRINOLOGY DIABETES AND METABOLISM CASE REPORTS
(2022)
Correction
Cardiac & Cardiovascular Systems
Gerald F. Watts, David R. Sullivan, David L. Hare, Karam M. Kostner, Ari E. Horton, Damon A. Bell, Tom Brett, Ronald J. Trent, Nicola K. Poplawski, Andrew C. Martin, Shubha Srinivasan, Robert N. Justo, Clara K. Chow, Jing Pang
AMERICAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2022)
Article
Medicine, General & Internal
Gerald F. Watts, David R. Sullivan, David L. Hare, Karam M. Kostner, Ari E. Horton, Damon A. Bell, Tom Brett, Ronald J. Trent, Nicola K. Poplawski, Andrew C. Martin, Shubha Srinivasan, Robert N. Justo, Clara K. Chow, Jing Pang
Summary: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, and new clinical practice recommendations aim to enhance the care of patients with FH by focusing on detection, diagnosis, management, and treatment. The core recommendations highlight the importance of risk stratification for personalized treatment plans, and comprehensive implementation science and practice strategies are needed to ensure proper dissemination of the guidance for the benefit of all families with FH.
INTERNAL MEDICINE JOURNAL
(2021)