Targeting immune cell recruitment in atherosclerosis.
Yvonne DöringEmiel P.C. van der VorstChristian WeberPublished in: Nature reviews. Cardiology (2024)
Atherosclerosis is the primary underlying cause of myocardial infarction and stroke. Atherosclerotic cardiovascular disease is characterized by a chronic inflammatory reaction in medium-to-large-sized arteries, with its onset and perpetuation driven by leukocytes infiltrating the subendothelial space. Activation of endothelial cells triggered by hyperlipidaemia and lipoprotein retention in the arterial intima initiates the accumulation of pro-inflammatory leukocytes in the arterial wall, fostering the progression of atherosclerosis. This inflammatory response is coordinated by an array of soluble mediators, namely cytokines and chemokines, that amplify inflammation both locally and systemically and are complemented by tissue-specific molecules that regulate the homing, adhesion and transmigration of leukocytes. Despite abundant evidence from mouse models, only a few therapies targeting leukocytes in atherosclerosis have been assessed in humans. The major challenges for the clinical translation of these therapies include the lack of tissue specificity and insufficient selectivity of inhibition strategies. In this Review, we discuss the latest research on receptor-ligand pairs and interactors that regulate leukocyte influx into the inflamed artery wall, primarily focusing on studies that used pharmacological interventions. We also discuss mechanisms that promote the resolution of inflammation and highlight how major findings from these research areas hold promise as potential therapeutic strategies for atherosclerotic cardiovascular disease.
Keyphrases
- cardiovascular disease
- peripheral blood
- oxidative stress
- inflammatory response
- endothelial cells
- cardiovascular risk factors
- cardiovascular events
- type diabetes
- cancer therapy
- mouse model
- atrial fibrillation
- physical activity
- heart failure
- left ventricular
- risk assessment
- machine learning
- high resolution
- vascular endothelial growth factor
- big data
- metabolic syndrome
- high throughput
- coronary artery disease
- brain injury
- single molecule
- climate change
- toll like receptor
- immune response
- blood flow
- binding protein
- cerebral ischemia
- mass spectrometry
- deep learning
- structural basis
- blood brain barrier
- cell adhesion
- cell migration
- case control