Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration

Cells. 2021 Mar 8;10(3):593. doi: 10.3390/cells10030593.

Abstract

Mural cells collectively refer to the smooth muscle cells and pericytes of the vasculature. This heterogenous population of cells play a crucial role in the regulation of blood pressure, distribution, and the structural integrity of the vascular wall. As such, dysfunction of mural cells can lead to the pathogenesis and progression of a number of diseases pertaining to the vascular system. Cardiovascular diseases, particularly atherosclerosis, are perhaps the most well-described mural cell-centric case. For instance, atherosclerotic plaques are most often described as being composed of a proliferative smooth muscle cap accompanied by a necrotic core. More recently, the role of dysfunctional mural cells in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, is being recognized. In this review, we begin with an exploration of the mechanisms underlying atherosclerosis and neurodegenerative diseases, such as mural cell plasticity. Next, we highlight a selection of signaling pathways (PDGF, Notch and inflammatory signaling) that are conserved across both diseases. We propose that conserved mural cell signaling mechanisms can be exploited for the identification or development of dual-pronged therapeutics that impart both cardio- and neuroprotective qualities.

Keywords: Alzheimer’s disease; atherosclerosis; cardiovascular disease; mural cells; neurodegeneration; pericytes; vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cardiotonic Agents / pharmacology
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Mice
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Neuroprotective Agents / pharmacology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Pericytes / drug effects*
  • Pericytes / metabolism
  • Pericytes / pathology
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction

Substances

  • Cardiotonic Agents
  • Neuroprotective Agents
  • Platelet-Derived Growth Factor
  • Receptors, Notch