Related Experiment Videos

PCSK9 as an Emerging Target for Cerebrovascular Dysfunction and Neuroinflammation in Ischemic Stroke

Carolina Vela1, Josephin Wagner1, Pal Pacher2

  • 1National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Clinical Center, Building 10 Room 3C710, 10 Center Drive, Bethesda, Maryland20892, United States.

ACS Chemical Neuroscience
|July 9, 2026
PubMed

Insights

Proprotein convertase subtilisin/kexin type 9 (PCSK9) drives stroke risk by promoting atherosclerosis and inflammation. PCSK9 inhibition shows promise in preclinical models for reducing ischemic injury and improving outcomes.

Area of Science:

  • Neuroscience
  • Cardiovascular Medicine
  • Genetics

Background:

  • Cerebrovascular disease, particularly ischemic stroke, is a major global health concern.
  • Atherosclerosis, characterized by lipid accumulation and inflammation, underlies most ischemic strokes.
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of lipid metabolism and vascular inflammation.

Purpose of the Study:

  • To investigate the role of PCSK9 in ischemic stroke pathogenesis.
  • To evaluate the therapeutic potential of PCSK9 inhibition (PCSK9i) in stroke models.

Main Methods:

  • Review of preclinical stroke models and clinical trial data.
  • Analysis of PCSK9's impact on atherogenesis, plaque stability, and thrombosis.
  • Assessment of PCSK9's role in vascular and neuroinflammation.

Main Results:

  • Elevated PCSK9 exacerbates ischemic injury by increasing LDL-C and promoting vascular inflammation.
  • PCSK9 contributes to neuroinflammation and secondary neuronal damage post-stroke.
  • PCSK9 inhibition demonstrated efficacy in preclinical models, reducing vascular and neuroinflammatory signaling.

Conclusions:

  • PCSK9 is a significant contributor to stroke risk and severity.
  • PCSK9 inhibition represents a promising therapeutic strategy for stroke prevention and treatment.
  • Clinical trials are exploring PCSK9i for cardiometabolic indications and neurological outcomes.

Keywords:
atherosclerotic plaque inflammationcerebrovascular diseaseischemic strokeneuroinflammationproprotein convertase subtilisin/kexin type 9 (PCSK9)

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
Ischemic Stroke l: Introduction01:15

Ischemic Stroke l: Introduction

Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
Ischemic Heart Disease: Overview01:17

Ischemic Heart Disease: Overview

Ischemic heart disease occurs when the heart's blood supply dwindles, causing an ominous lack of oxygen and nutrients. This deficiency, stemming from reduced or obstructed blood flow, spells danger, leading to heart muscle damage and dysfunction.
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and narrowing...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Hemorrhagic Stroke ll: Pathophysiology01:29

Hemorrhagic Stroke ll: Pathophysiology

A hemorrhagic stroke develops when a cerebral blood vessel ruptures, allowing blood to escape into the surrounding brain tissue, as in intracerebral hemorrhage (ICH), or into the subarachnoid space, as in subarachnoid hemorrhage (SAH). Because the skull is a rigid compartment, the sudden presence of extravascular blood rapidly increases intracranial pressure and compresses adjacent neural structures, leading to immediate tissue injury and impaired cerebral perfusion.Mass Effect and Primary...