Article
Medicine, General & Internal
Jonathan Grimm, Georg Peschel, Martina Mueller, Doris Schacherer, Reiner Wiest, Kilian Weigand, Christa Buechler
Summary: This study found that serum PCSK9 levels were associated with liver injury and inflammation in cirrhotic HCV patients, but not with LDL levels. After DAA therapy, PCSK9 decreased and LDL increased in non-cirrhotic HCV patients, while no changes were observed in the cirrhotic group.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Vittoria Cammisotto, Francesco Baratta, Paola G. Simeone, Cristina Barale, Enrico Lupia, Gioacchino Galardo, Francesca Santilli, Isabella Russo, Pasquale Pignatelli
Summary: PCSK9 is involved in cholesterol metabolism and plays a role in the development of atherosclerosis and atherothrombotic processes, promoting plaque formation and oxidative stress.
Article
Cardiac & Cardiovascular Systems
Alex K. K. Leung, Yuan Chao Xue, Antyrah de Guzman, Guilherme Grzelkovski, HyeJin Julia Kong, Kelly R. Genga, James A. Russell, John H. Boyd, Gordon A. Francis, Keith R. Walley
Summary: This study found that PCSK9 reduces the uptake of LPS in vascular endothelial cells through LDLR-mediated endocytosis, leading to a decrease in the inflammatory response. This suggests that PCSK9 inhibition may have additional effects on vascular endothelial inflammation.
Article
Cardiac & Cardiovascular Systems
Coen van Solingen, Scott R. Oldebeken, Alessandro G. Salerno, Amarylis C. B. A. Wanschel, Kathryn J. Moore
Summary: The discovery of PCSK9 and its role in LDL regulation has led to the rapid development of therapeutic PCSK9 inhibitors. Research has identified certain microRNAs that can reduce PCSK9 expression, leading to increased LDLR expression in hepatic cells, which may have therapeutic implications for manipulating LDLR expression and cholesterol levels in the liver.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Anindita Chakraborty, Jing Pang, Dick C. Chan, Wendy Barnett, Ann Marie Woodward, Mary Vorster, Gerald F. Watts
Summary: PCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice, with significant reductions in LDL-C, remnant-cholesterol, and apolipoprotein B concentrations as well.
CLINICAL CARDIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Po-Wei Chen, Shih-Ya Tseng, Hsien-Yuan Chang, Cheng-Han Lee, Ting-Hsing Chao
Summary: The study reveals that Cilostazol can regulate the expression of PCSK9 through enhancing the PPARγ pathway, thus impacting cholesterol homeostasis. It was observed that Cilostazol significantly reduces PCSK9 levels in high-fat diet-induced obese mice and obese patients, indicating its therapeutic potential for obesity-related dyslipidemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Xiaole Chang, Yongfang Zhao, Shucun Qin, Hao Wang, Bingxiang Wang, Lei Zhai, Boyan Liu, Hong-mei Gu, Da-wei Zhang
Summary: The adrenal gland in Surf4(LKO) mice shows reduced cholesterol levels and increased expression of genes involved in de novo cholesterol biosynthesis, leading to compensation for the loss of circulating lipoprotein-derived cholesterol and maintenance of adrenal steroid hormone production.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Chemistry, Medicinal
Niki Katsiki, Michal Vrablik, Maciej Banach, Ioanna Gouni-Berthold
Summary: Dyslipidemia treatment is crucial for reducing the risk of ASCVD, the leading cause of death worldwide. PCSK9 inhibitors, including inclisiran, have emerged as a novel category of lipid-lowering drugs. Inclisiran, a siRNA against PCSK9, has been approved for treating hypercholesterolemia and offers a long-lasting LDL-C-lowering effect with just two doses per year. The ORION/VICTORION clinical trial program investigates the impact of inclisiran on atherogenic lipoproteins and major cardiac events in different patient populations.
Article
Medical Laboratory Technology
Antonin Jabor, Tereza Vackova, Zdenek Kubicek, Jitka Komrskova, Marek Protus, Janka Franekova
Summary: The study evaluated the biological variation of serum PCSK9, finding a high within-subject variability in healthy individuals, suggesting that common reference intervals can be used to interpret its values.
CLINICA CHIMICA ACTA
(2021)
Review
Biochemistry & Molecular Biology
Gregory G. Schwartz, Robert P. Giugliano
Summary: This review summarizes the findings of two large placebo-controlled trials that evaluated the cardiovascular efficacy of PCSK9 inhibitors in patients with established ASCVD or recent ACS. The results showed that PCSK9 inhibitors can significantly reduce MACE risk and may also reduce the risk of death after ACS.
CURRENT OPINION IN LIPIDOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Petra Zubin Maslov, Joseph A. Hill, Thomas F. Luscher, Jagat Narula
Summary: Hypercholesterolaemia is a significant risk factor for cardiovascular disease, with cholesterol levels already increasing in early life. In the USA, only 25% of infants are exclusively breastfed, and formula feeding may lead to fluctuations in blood glucose and insulin levels in infants.
EUROPEAN HEART JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Rabia Aydogan Baykara, Pinar Diydem Yilmaz, Mevlut Hakan Goktepe, Cengiz Kadiyoran, Mustafa Ogul, Adem Kucuk, Medine Cumhur Cure, Erkan Cure
Summary: There is a strong independent association between subclinical atherosclerosis and PCSK9 in patients with Behcet's disease. However, there may be no independent association between PCSK9 and disease activity.
CLINICAL AND EXPERIMENTAL HYPERTENSION
(2022)
Review
Cardiac & Cardiovascular Systems
Yimo Zhou, Weiqi Chen, Meng Lu, Yongjun Wang
Summary: This meta-analysis found a significant association between high circulating PCSK9 concentration and the risk of MACEs, with a linear dose-response relationship observed. However, no significant correlation was found with stroke or all-cause mortality. Further well-designed studies are needed to explore the relationships between PCSK9 concentration and stroke and mortality.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
Sara N. Levintow, Stephanie R. Reading, Sina Noshad, Sophie E. Mayer, Catherine Wiener, Bassim Eledath, Jason Exter, M. Alan Brookhart
Summary: The study found that LDL-C testing rates were lower than recommended by clinical guidelines among patients hospitalized for myocardial infarction. This highlights a potential gap in care, where increased LDL-C testing after MI may provide opportunities for modifying lipid-lowering therapies and reducing the risk of subsequent cardiovascular events.
CLINICAL EPIDEMIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Deepika Maliwal, Raghuvir R. S. Pissurlenkar, Vikas Telvekar
Summary: PCSK9 is involved in regulating lipoprotein metabolism and its inhibitors can lower cholesterol levels. Small molecules with potential to inhibit PCSK9 have been identified and assessed for their pharmacokinetics, toxicity profiles, and binding interactions, making them promising candidates for further development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cardiac & Cardiovascular Systems
Anjali B. Thakkar, Yifei Ma, Mark Dela Cruz, Yuaner Wu, Victor Arechiga, Shreya Swaminathan, Peter Ganz, Alan H. B. Wu, Rebecca Scherzer, Steven Deeks, Priscilla Y. Hsue
Summary: HIV infection affects the balance between levels of ANG1 and ANG2, leading to endothelial dysfunction. Treatment status may alter this balance, and HIV promotes endothelial dysfunction through microvascular impairment.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Environmental Sciences
M. W. Frampton, J. R. Balmes, P. A. Bromberg, M. Arjomandi, M. J. Hazucha, S. W. Thurston, N. E. Alexis, P. Ganz, W. Zareba, P. Koutrakis, K. Thevenet-Morrison, D. Q. Rich
Summary: The study found associations between increased ambient PM2.5, NO2, and CO levels and reduced pulmonary function, as well as increased ambient ozone concentrations and reduced heart rate variability (HRV). However, there was improvement in pulmonary function and HRV during the exposure sessions, suggesting a recovery effect. These findings support the link between short term increases in ambient PM2.5, NO2, and CO and decreased pulmonary function, as well as increased ambient ozone and decreased HRV.
ENVIRONMENTAL RESEARCH
(2022)
Article
Immunology
Jeffrey A. Tomalka, Mehul S. Suthar, Steven G. Deeks, Rafick Pierre Sekaly
Summary: Host genetic and environmental factors play a significant role in vaccine-induced immune responses. Understanding and accounting for these factors are crucial for the development of effective vaccines against SARS-CoV-2.
Article
Medicine, Research & Experimental
Akif Altinbas, Jacinta A. Holmes, Shadi Salloum, Anna Lidofsky, Nadia Alatrakchi, Ma Somsouk, Peter Hunt, Steven Deeks, Kara W. Chew, Georg Lauer, Annie Kruger, Wenyu Lin, Raymond T. Chung
Summary: This study assessed the relationship between LOXL-2 and TNC-C levels and fibrosis severity in HIV and/or HCV-infected individuals. The study found that LOXL-2 and TNC-C levels were significantly higher in individuals with intermediate fibrosis in HCV and HCV/HIV co-infected individuals.
BIOMARKERS IN MEDICINE
(2022)
Editorial Material
Cell Biology
Stephen A. Williams, Peter Ganz
Summary: A 27-protein signature has been proposed as a predictive tool for cardiovascular disease, and its suitability in specific clinical decision-making situations is discussed.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Geriatrics & Gerontology
Anne B. Newman, Sheena Patel, Jorge R. Kizer, Se-Jin Lee, Shalinder Bhasin, Peggy Cawthon, Nathan LeBrasseur, Russel P. Tracy, Peter Ganz, Steven R. Cummings
Summary: Studies using heterochronic parabiosis have found that circulating factors play a role in brain aging in animal models. In this study, the levels of GDF-11, GDF-8, and follistatin were evaluated and their associations with cognitive function, brain MRI findings, and incident dementia were assessed. The results showed that these factors were not significantly correlated with cognitive outcomes or dementia in older adults.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Rajat Deo, Ruth F. Dubin, Yue Ren, Ashwin C. Murthy, Jianqiao Wang, Haotian Zheng, Zihe Zheng, Harold Feldman, Haochang Shou, Josef Coresh, Morgan Grams, Aditya L. Surapaneni, Zeenat Bhat, Jordana B. Cohen, Mahboob Rahman, Jiang He, Santosh L. Saraf, Alan S. Go, Paul L. Kimmel, Ramachandran S. Vasan, Mark R. Segal, Hongzhe Li, Peter Ganz
Summary: Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models for patients with chronic kidney disease (CKD). The proteomic risk model outperformed traditional clinical models in predicting cardiovascular risk and provided new biological insights for the development of cardiovascular risk management strategies in CKD patients.
EUROPEAN HEART JOURNAL
(2023)
Review
Microbiology
Raphael J. Landovitz, Hyman Scott, Steven G. Deeks
Summary: In this Review, the authors explore the current state of HIV prevention and treatment, highlighting unmet needs and emerging tools. They discuss the combination of different approaches to achieve better outcomes, and describe recent progress in pre-exposure prophylaxis, vaccines, treatment, and cure. They emphasize the need for continued efforts to develop effective preventative vaccines and scalable cures, as the limitations of antiretroviral drugs become more apparent.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Hyunju Kim, Alice H. Lichtenstein, Peter Ganz, Shutong Du, Olive Tang, Bing Yu, Nilanjan Chatterjee, Lawrence J. Appel, Josef Coresh, Casey M. Rebholz
Summary: This study identified 19 proteins associated with the DASH diet, which may serve as biomarkers. The results suggest potential pathways impacted by the consumption of the DASH diet.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Geriatrics & Gerontology
Jorge R. Kizer, Sheena Patel, Peter Ganz, Anne B. Newman, Shalender Bhasin, Se-Jin Lee, Peggy M. Cawthon, Nathan K. LeBrasseur, Sanjiv J. Shah, Bruce M. Psaty, Russell P. Tracy, Steven R. Cummings
Summary: This study suggests that serum follistatin and FSTL-3, but not GDF-11 or GDF-8, are associated with incident heart failure in older adults, implicating transforming growth factor-beta superfamily pathways as potential therapeutic targets.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks, Michel C. Nussenzweig
Summary: Most proviruses in people living with HIV are defective, but intact proviruses can lead to viral rebound. The two-probe intact proviral DNA assay (IPDA) found 40-fold more intact proviruses compared to the near full length (nfl) Q4PCR. Both assays showed that defective proviruses did not decay over 10 years. However, the average half-lives of intact proviruses were different: 108 months for IPDA and 65 months for Q4PCR. Misclassified defective proviruses and very long-lived intact proviruses could explain this difference.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Charline Bacchus-Souffan, Mark Fitch, Mohamed Abdel-Mohsen, Rebecca Hoh, Haelee Ahn, Mars Stone, Frederick Hecht, Jeffrey Martin, Steven G. Deeks, Marc K. Hellerstein, Joseph M. McCune, Joshua T. Schiffer, Peter W. Hunt
Summary: The persistence of HIV in people on suppressive antiretroviral therapy is linked to physiological mechanisms of CD4+ T cells. This study investigates the longitudinal kinetics of HIV DNA and cell turnover rates in different CD4 cell subsets. The results indicate that HIV clears faster in more proliferative/differentiated CD4 cell subsets and therapies targeting proliferation and differentiation may reduce HIV DNA levels.
NATURE COMMUNICATIONS
(2023)
Article
Medical Laboratory Technology
Ruth F. Dubin, Rajat Deo, Yue Ren, Hongzhe Lee, Haochang Shou, Harold Feldman, Paul Kimmel, Sushrut S. Waikar, Eugene P. Rhee, Adrienne Tin, Jingsha Chen, Joseph Coresh, Alan S. Go, Tanika Kelly, Paduranga S. Rao, Teresa K. Chen, Mark R. Segal, Peter Ganz
Summary: A study was conducted to evaluate the analytical and biological variability of the aptamer proteomic assay, SomaScan V4, in patients with moderate to severe chronic kidney disease (CKD). The study found that the variability of the assay in CKD patients was low and similar to individuals without CKD.
JOURNAL OF APPLIED LABORATORY MEDICINE
(2023)
Article
Endocrinology & Metabolism
Nisha Parikh, Folagbayi Arowolo, Matthew S. Durstenfeld, Gregory Nah, Joyce Njoroge, Eric Vittinghoff, Carlin S. Long, Peter Ganz, David Pearce, Priscilla Hsue, Alan H. S. Wu, Negin Hajizadeh, Kathleen D. Liu, Kara L. Lynch
Summary: This study aimed to determine the differences in circulating RAAS biomarker levels between COVID-19 patients and non-COVID-19 patients throughout the disease course. The results showed that a high ARR may be a risk marker for COVID-19 hospitalization, independent of BMI. Serum ACE activity was lower in COVID-19 patients compared to controls at the beginning of hospitalization and then increased to similar levels as controls, possibly due to lung injury, which improved with inpatient disease management.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)