Related Experiment Video
Updated: Feb 7, 2026
08:14
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
8.6K
The Evolving Future of PCSK9 Inhibitors
Robert S Rosenson1, Robert A Hegele2, Sergio Fazio3
1Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, New York.
Journal of the American College of Cardiology
|July 18, 2018
Summary
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease events. These PCSK9 therapies demonstrate a favorable safety profile, supporting their use in high-risk patients.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pharmacology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) variants influence low-density lipoprotein (LDL) regulation.
- PCSK9 plays a critical role in cholesterol metabolism and cardiovascular risk.
Purpose of the Study:
- To evaluate the efficacy and safety of PCSK9 inhibitors in lowering LDL cholesterol.
- To assess the impact of PCSK9 inhibition on atherosclerotic cardiovascular disease (ASCVD) events.
Main Methods:
- Analysis of clinical trial data involving human monoclonal antibodies targeting PCSK9.
- Assessment of LDL-C reduction and ASCVD event rates in various high-risk patient cohorts.
Main Results:
- PCSK9 inhibitors achieved 55%-72% LDL-C reduction in high-risk patients.
- Profound LDL-C lowering (<25 mg/dl) correlated with reduced ASCVD events, suggesting no lower limit.
- PCSK9 inhibitor therapy demonstrated a favorable safety profile.
Conclusions:
- PCSK9 inhibition is effective in significantly lowering LDL-C and reducing ASCVD events.
- Aggressive LDL-C lowering with PCSK9 inhibitors is safe and recommended for high-risk individuals.
- Evidence supports PCSK9 inhibitors for high-risk patients with LDL-C ≥70 mg/dl on maximally tolerated oral therapies.
Related Concept Videos
01:52Eukaryotic Transcription Inhibitors
11.0K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
01:23Dipeptidyl Peptidase 4 Inhibitors
686
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
686
01:25Antihypertensive Drugs: Direct Renin Inhibitors
1.5K
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
1.5K
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.6K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.6K
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
615
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
615
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
583
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
Acarbose and miglitol are...
583