The lectin-like oxidized low-density lipoprotein receptor-1 as therapeutic target for atherosclerosis, inflammatory conditions and longevity

Abstract

Introduction: The lectin-like oxidized LDL receptor-1 (LOX-1) is a scavenger receptor and is regarded as a central element in the initiation of endothelial dysfunction and its further progression to atherosclerosis. Increasing numbers of studies suggest that therapeutic strategies to modulate LOX-1 will have a broad spectrum of applications ranging from cardiovascular diseases to longevity.

Areas covered: The dual role of LOX-1 as a culprit molecule in the process of atherosclerosis and as a danger signal in various tissues is introduced. The structure of the receptor, its ligands and its modulation by known drugs, by natural products (e.g., statins, imipramine, salicylate-based drugs, procyanidins, curcumin) and by new strategies (antisenseRNA, miRNA, pyrrole-imidazol-polyamides, LOX-1 antibodies, lipid apheresis) are described.

Expert opinion: Therapeutic approaches via transcript regulation, allowing a modulation of LOX-1, may be an easier and safer strategy than a blockade of the receptor. Considering the wide distribution of LOX-1 on different tissues, research on the mechanisms of LOX-1 modulation by drugs and natural products applying “omic”-technologies will not only allow a better understanding of the role of LOX-1 in the processes of atherosclerosis, inflammation and longevity but also support the development of specific LOX-1 modulators, avoiding the initiation of molecular mechanisms which lead to adverse events.

Keywords::

• atherosclerosis
• cardiovascular diseases
• imipramine
• inflammation
• LOX-1 antibodies
• LOX-1 receptor
• omics
• salicyclic acid

Acknowledgments

Authors thank the Informa Healthcare publishers for language editing. Authors are also thankful to B Merzenich and S Singh for graphical design and the reviewers for their excellent comments.

Notes

This box summarizes key points contained in the article.