Article
Hematology
Yong-Xiang Chen, Chunhua Shi, Jingti Deng, Catherine Diao, Nadia Maarouf, Matthew Rosin, Vipul Shrivastava, Angie A. Hu, Sonya Bharadwa, Ayinuer Adijiang, Annegret Ulke-Lemee, Brenig Gwilym, Alexandria Hellmich, Christopher Malozzi, Zarah Batulan, Jonathan L. E. Dean, F. Daniel Ramirez, Jingwen Liu, William T. Gerthoffer, Edward R. O'Brien
Summary: The study demonstrates that HSP27 immunotherapy can lower cholesterol and PCSK9 levels primarily by increasing LDLR expression, and is associated with significant reductions in inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Arjen J. Cupido, Laurens F. Reeskamp, Aroon D. Hingorani, Chris Finan, Folkert W. Asselbergs, G. Kees Hovingh, Amand F. Schmidt
Summary: This study explored the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease and other clinical and safety outcomes. The results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD.
Article
Hematology
Fan-Hua Meng, Shuai Liu, Jian Xiao, Yu-Xia Zhou, Le-Wei Dong, Yun-Feng Li, Yan-Qing Zhang, Wei-Hui Li, Ju-Qiong Wang, Yan Wang, Bao-Liang Song, Yi-Tong Ma, Zhen-Yan Fu, Jie Luo
Summary: Two PCSK9 mutations, E144K and C378W, were identified in Chinese Uyghurs, which are associated with low plasma levels of LDL-C. These mutations impair the maturation and secretion of the PCSK9 protein, leading to increased LDL receptor levels in the liver and decreased LDL-C levels in the serum. This study suggests that these mutations may also be present in humans.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Khadijeh Mahboobnia, Matteo Pirro, Ettore Marini, Francesco Grignani, Evgeny E. Bezsonov, Tannaz Jamialahmadi, Amirhossein Sahebkar
Summary: PCSK9 plays an important role in the development and progression of various cancers, highlighting its potential significance in cancer treatment. Inhibiting PCSK9 may help suppress the proliferation and invasion of tumor cells. However, the current lack of data on the role of PCSK9 in cancer and the impact of PCSK9 inhibition in cancer therapy limits our understanding of its effectiveness and safety.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Tadeja Sotler, Miran Sebestjen
Summary: Disturbances in lipid metabolism are a major risk factor for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important protein in lipid metabolism that is also involved in inflammation, endothelial dysfunction, and atherosclerotic plaque development. PCSK9 has been linked to inflammation and plays a role in the initiation and development of atherosclerotic lesions. Experimental studies have shown that an increased concentration of PCSK9 accelerates endothelial cell apoptosis and impairs endothelial function, creating conditions for the development of atherosclerosis. PCSK9 inhibitors can improve clinical outcomes through both lipid-dependent and lipid-independent pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Carlota Oleaga, Michael D. Shapiro, Joshua Hay, Paul A. Mueller, Joshua Miles, Cecilia Huang, Emily Friz, Hagai Tavori, Peter P. Toth, Cezary Wojcik, Bruce A. Warden, Jonathan Q. Purnell, P. Barton Duell, Nathalie Pamir, Sergio Fazio
Summary: This study investigated the mechanisms behind the increase in plasma PCSK9 levels in response to PCSK9i therapy. The findings suggest that PCSK9i enhances PCSK9 secretion, contributing to the elevated plasma PCSK9 levels in treated subjects.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Nutrition & Dietetics
Aisha A. Siddiq, Asha Martin
Summary: This study found that crocetin inhibits the expression of PCSK9, increases the expression of hepatic LDL receptor, and decreases the expression of SREBPs. It also regulates the expression of sortilin involved in PCSK9 transport. These findings suggest that crocetin has potential therapeutic effects in reducing cholesterol levels.
NUTRITION RESEARCH
(2022)
Article
Cell Biology
Peter Gennemark, Katrin Walter, Niclas Clemmensen, Dinko Rekic, Catarina A. M. Nilsson, Jane Knochel, Mikko Holtta, Linda Wernevik, Birgitta Rosengren, Dorota Kakol-Palm, Yanfeng Wang, Rosie Z. Yu, Richard S. Geary, Stan J. Riney, Brett P. Monia, Rikard Isaksson, Rasmus Jansson-Lofmark, Cristina S. J. Rocha, Daniel Linden, Eva Hurt-Camejo, Rosanne Crooke, Lloyd Tillman, Tina Ryden-Bergsten, Bjorn Carlsson, Ulf Andersson, Marie Elebring, Anna Tivesten, Nigel Davies
Summary: In this study, a chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery was developed and shown to effectively reduce LDL cholesterol levels. Animal experiments demonstrated liver targeting and significant reductions in PCSK9 and LDL cholesterol levels after oral administration.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Nurjannatul Naim Kamaruddin, Nor Azwin Hajri, Yosie Andriani, Aina Farahiyah Abdul Manan, Tengku Sifzizul Tengku Muhammad, Habsah Mohamad
Summary: Atherosclerosis, caused by elevated plasma cholesterols, is a major factor in global cardiovascular disease mortality. While statins are commonly used to lower cholesterol levels, they may have adverse effects, prompting the search for new treatments. Research on the marine invertebrate Acanthaster planci suggests its potential in reducing cholesterol levels without causing harm to the liver.
Article
Cardiac & Cardiovascular Systems
Michelle L. O'Donoghue, Robert P. Giugliano, Stephen D. Wiviott, Dan Atar, Anthony Keech, Julia F. Kuder, KyungAh Im, Sabina A. Murphy, Jose H. Flores-Arredondo, J. Antonio G. Lopez, Mary Elliott-Davey, Bei Wang, Maria Laura Monsalvo, Siddique Abbasi, Marc S. Sabatine
Summary: Long-term use of evolocumab to lower LDL-C levels is associated with low rates of adverse events, which do not exceed those in the placebo group. Over time, the use of evolocumab also leads to further reduction in cardiovascular events.
Review
Biochemistry & Molecular Biology
Daniela Passarella, Maurizio Ronci, Valentina Di Liberto, Mariachiara Zuccarini, Giuseppa Mudo, Carola Porcile, Monica Frinchi, Patrizia Di Iorio, Henning Ulrich, Claudio Russo
Summary: Recent studies have found that cerebral cholesterol formation is primarily controlled by astrocytes, which synthesize cholesterol and deliver it to neurons and oligodendrocytes through specific lipoprotein receptors. Various proteins and carbohydrates modulate the cholesterol shuttle, affecting lipoprotein receptor activity, function, and signaling. Purine receptors, particularly subtypes P2Y(2), P2X(7), and A(2A), play a role in neurodegenerative diseases such as Alzheimer's and Niemann-Pick C diseases by regulating brain cholesterol homeostasis. The precise mechanisms of these interactions are not well understood, but further research in the cholesterol-purine reciprocal control is warranted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Nurjannatul Naim Kamaruddin, Lukman Hakim Mohd Din, Allicia Jack, Aina Farahiyah Abdul Manan, Habsah Mohamad, Tengku Sifzizul Tengku Muhammad
Summary: This study investigated the effects of a selected fraction of A. planci on PCSK9 gene expression, LDLR protein level, and LDL-C uptake. The results showed that the selected fraction reduced PCSK9 gene expression, increased LDLR protein level, and promoted LDL-C uptake. These findings suggest that the selected fraction has the potential to lower circulating LDL-C levels and may be a promising therapeutic intervention for preventing the progression of atherosclerosis.
Article
Behavioral Sciences
Andrew S. Bell, Josephin Wagner, Daniel B. Rosoff, Falk W. Lohoff
Summary: The gene encoding PCSK9 and its protein product have been widely studied for their role in cholesterol and lipid metabolism. There is a growing body of evidence that PCSK9 plays a crucial role in pathogenic processes in other organ systems, including the central nervous system. PCSK9's impact on the brain is not yet fully understood, but recent studies have sought to illuminate its connection with neurodegenerative and psychiatric disorders. The review aims to describe PCSK9's role in the central nervous system, examine its potential in disease outcomes, and explore the clinical potential of PCSK9 inhibitors and genetic variation in the PCSK9 gene.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Palak P. Oza, Khosrow Kashfi
Summary: Cancer is a global burden that affects premature mortality, productivity loss, healthcare expenditures, and mental health. Recent research has revealed a new role for cholesterol-lowering PCSK9 inhibitors in cancer treatment. PCSK9 is an enzyme that degrades LDL receptors, responsible for cholesterol clearance. By inhibiting PCSK9, LDL receptors are upregulated, leading to cholesterol reduction. The cholesterol-lowering effects of PCSK9 inhibitors have potential in combating cancer growth and enhancing existing anticancer therapies.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Jasmine Phenix, Jonathan Cote, Denis Dieme, Sherilyn J. Recinto, Felix Oestereich, Sasen Efrem, Sami Haddad, Michele Bouchard, Lisa Marie Munter
Summary: High levels of plasma cholesterol, especially LDL-C, have been associated with an increased risk of Alzheimer's disease. Decreased CETP activity has been linked to better cognitive performance and a lower risk of Alzheimer's disease. CETP inhibitors, such as evacetrapib, can enter the brain and may be a potential treatment for CETP-mediated cholesterol dysregulation in Alzheimer's disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Engineering, Biomedical
Cassandra Su Lyn Ho, Toshikatsu Horiuchi, Hiroaki Taniguchi, Araya Umetsu, Kohsuke Hagisawa, Keiichi Iwaya, Kanji Nakai, Amalina Azmi, Natasha Zulaziz, Azran Azhim, Nariyoshi Shinomiya, Yuji Morimoto
BIOMEDICAL ENGINEERING ONLINE
(2016)
Article
Critical Care Medicine
Kohsuke Hagisawa, Manabu Kinoshita, Hiroki Miyawaki, Shunichi Sato, Hiromi Miyazaki, Shinji Takeoka, Hidenori Suzuki, Keiichi Iwaya, Shuhji Seki, Satoshi Shono, Daizoh Saitoh, Yasuhiro Nishida, Makoto Handa
CRITICAL CARE MEDICINE
(2016)
Review
Physiology
Yasuhiro Nishida, Satoshi Maruyama, Ichiro Shouji, Takehito Kemuriyama, Akimasa Tashiro, Hiroyuki Ohta, Kohsue Hagisawa, Megumi Hiruma, Hidetake Yokoe
JOURNAL OF PHYSIOLOGICAL SCIENCES
(2016)
Article
Critical Care Medicine
Kohsuke Hagisawa, Manabu Kinoshita, Bonpei Takase, Kenichi Hashimoto, Daizoh Saitoh, Shuhji Seki, Yasuhiro Nishida, Hiromi Sakai
Article
Chemistry, Organic
Shimpei Iwaki, Kazuya Hokamura, Mikako Ogawa, Yasuo Takehara, Yasuaki Muramatsu, Takehiro Yamane, Kazuhisa Hirabayashi, Yuji Morimoto, Kohsuke Hagisawa, Kazuhide Nakahara, Tomoko Mineno, Takuya Terai, Toru Komatsu, Tasuku Ueno, Keita Tamura, Yusuke Adachi, Yasunobu Hirata, Makoto Arita, Hiroyuki Arai, Kazuo Umemura, Tetsuo Nagano, Kenjiro Hanaoka
ORGANIC & BIOMOLECULAR CHEMISTRY
(2014)
Article
Hematology
Kohsuke Hagisawa, Kahoko Nishikawa, Rempei Yanagawa, Manabu Kinoshita, Mami Doi, Hidenori Suzuki, Keiichi Iwaya, Daizoh Saitoh, Shuhji Seki, Shinji Takeoka, Makoto Handa, Yasuhiro Nishida
Article
Hematology
Kohsuke Hagisawa, Manabu Kinoshita, Masato Takikawa, Shinji Takeoka, Daizoh Saitoh, Shuhji Seki, Hiromi Sakai
Article
Hematology
Kohsuke Hagisawa, Manabu Kinoshita, Daizoh Saitoh, Yuji Morimoto, Hiromi Sakai
Article
Multidisciplinary Sciences
Osamu Ishida, Kohsuke Hagisawa, Nozomu Yamanaka, Koji Tsutsumi, Hidenori Suzuki, Masato Takikawa, Shinji Takeoka, Manabu Kinoshita
SCIENTIFIC REPORTS
(2020)
Article
Obstetrics & Gynecology
Yukako Yuki, Kohsuke Hagisawa, Manabu Kinoshita, Hiroki Ishibashi, Kouki Kaneko, Osamu Ishida, Daizoh Saitoh, Hiromi Sakai, Katsuo Terui
Summary: Hemoglobin vesicle infusion may be effective in the initial management of massive obstetric hemorrhage, maintaining adequate mean arterial pressure and hemoglobin concentration, thereby preventing an increase in lactate levels and improving survival rates.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2021)
Article
Clinical Neurology
Motoyuki Jitsu, Katsuki Niwa, Go Suzuki, Takeyuki Obara, Yukiko Iwama, Kohsuke Hagisawa, Yukihiro Takahashi, Yoshitaro Matsushita, Satoru Takeuchi, Hiroshi Nawashiro, Shunichi Sato, Satoko Kawauchi
Summary: By applying laser-induced shock waves to rat brains, it was found that exposure to higher impulse shock waves led to behavioral deficits and axonal injury, with a significant correlation between axonal density reduction in certain brain regions and depression-like behaviors.
FRONTIERS IN NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Hiroki Ishibashi, Kohsuke Hagisawa, Manabu Kinoshita, Yukako Yuki, Morikazu Miyamoto, Tomoko Kure, Hiromi Sakai, Daizoh Saitoh, Katsuo Terui, Masashi Takano
Summary: In a pregnant rabbit model, HbV infusion effectively prevents lethal hemorrhagic shock in severe PPH, with 8 out of 10 rabbits surviving for 6 hours. While no rabbits survived beyond 6 hours with HES infusion alone, all rabbits receiving RBC/PPP transfusion survived.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Kohsuke Hagisawa, Manabu Kinoshita, Shinji Takeoka, Osamu Ishida, Yayoi Ichiki, Daizoh Saitoh, Morihiro Hotta, Masato Takikawa, Ivo P. Torres Filho, Yuji Morimoto
Summary: The study evaluated the hemostatic efficacy of fibrinogen gamma-chain (H12)-coated liposomes in thrombocytopenic rabbits, showing that treatment with H12-(ADP)-liposomes followed by RBC/PPP or RBC/PRP effectively stopped bleeding and improved survival rates.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Proceedings Paper
Automation & Control Systems
C. Ho, T. Horiuchi, H. Taniguchi, A. Umetsu, K. Hagisawa, K. Iwaya, A. Azmi, N. Zulaziz, A. Azhim, N. Shinomiya, Y. Morimoto
2015 10TH ASIAN CONTROL CONFERENCE (ASCC)
(2015)