Researchers discover a cell type responsible for cardiac repair after infarction

October 13, 2020

The researcher of the Faculty of Science of the UMA Adrián Ruiz-Villalba, who is also member of the Andalusian Center for Nanomedicine and Biotechnology (BIONAND) and the Biomedical Research Institute of Malaga (IBIMA), is the first author of an international study that has identified the heart cells in charge of repairing the damage caused to this organ after infarction. This study has been recently published in the American Heart Association journal Circulation, first in the world dedicated to cardiovascular research.

These "reparative" cells consist in a population of cardiac fibroblasts that play a crucial role in generating the collagenous scar required to prevent ventricular wall rupture. This research, carried out with scientists from the Center for Applied Medical Research of Pamplona (CIMA) and the University Clinic of Navarra, also reveals the molecular mechanisms that activate these cells and regulate their function.

This discovery, according to the researchers, will enable the identification of new therapeutic targets and the development of targeted therapies to control the cardiac repair process following infarction.

Characterization of reparative cardiac fibroblasts

Cardiac fibroblasts are one of the essential components of the heart. These cells play a key role in maintaining the structure and mechanics of this vital organ. "Recent studies have shown that fibroblasts do not respond homogeneously to heart injury, so the purpose of our study was to define their heterogeneity during ventricular remodeling and understand the mechanisms that regulate the function of these cells", explains Felipe Prósper, researcher of CIMA and the University Clinic of Navarra.

"Through single-cell transcriptomics (single-cell RNA-seq analysis) we identified a subpopulation within cardiac fibroblasts that we named Reparative Cardiac Fibroblasts (RCF) for their role after cardiac injury. We verified that, when a patient suffers a heart attack, these RCF activate to provide a fibrotic response that generates a collagenous scar that prevents heart tissue rupture", says the researcher, who is also member of the Cell Therapy Network (TerCel) and the Health Research Institute of Navarra (IdiSNA).

CTHRC1, a protein related to the collagen that is essential for the healing process

At a molecular level, these scientists have discovered that RCF are characterized by a unique transcriptional profile, that is, a specific information pattern for the expression of the genes involved in their cardiac function. "Among the main differential markers of the transcriptome of these cells we identified the CTHRC1 protein (Collagen Triple Helix Repeat Containing 1), a molecule that is essential in the fibrotic response after myocardial infarction. Specifically, this protein participates in the collagen synthesis of the cardiac extracellular matrix and is crucial to the ventricular remodeling process", says the researcher Adrián Ruiz-Villalba.

According to Ruiz-Villalba, these results suggest that RCF activate the cicatrization of cardiac injuries by segregating the CTHRC1 protein. Therefore, this molecule could be considered as a biomarker associated with the physiologic state of a damaged heart and a potential therapeutic target for patients that have had a myocardial infarction or that suffer from dilated cardiomyopathy.

This study falls within the line of research on cardiac fibrosis of the "Cardiovascular Development and Angiogenesis" group led by José María Pérez Pomares, professor of the Department of Animal Biology of the Faculty of Science of the UMA. This group studies the cellular and molecular mechanisms that underlie this type of pathologies by using different animal models and collaborating with different basic and clinical teams, both national and international.

'Single-Cell RNA-seq Analysis Reveals a Crucial Role for Collagen Triple Helix Repeat Containing 1 (CTHRC1) Cardiac Fibroblasts after Myocardial Infarction' is the result of five years of work, which comprises more than 30 different authors. Likewise, other R&D&I centers have participated in the study, such as NavarraBiomed (Pamplona), Maine Medical Center Research Institute (USA), CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences (Vienna) and KU Leuven (Belgium).

Ruiz-Villalba A. et al. Single-Cell RNA-seq Analysis Reveals a Crucial Role for Collagen Triple Helix Repeat Containing 1 (CTHRC1) Cardiac Fibroblasts after Myocardial Infarction. Circulation. 2020 Sep 25. Doi: 10.1161/CIRCULATIONAHA.119.044557

University of Malaga

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to