Crosstalk of human coronary perivascular adipose-derived stem cells with vascular cells: role of tissue factor.
Gemma ArderiuMaria Teresa BejarAnna Civit-UrgellEsther PeñaLina BadimonPublished in: Basic research in cardiology (2024)
The coronary perivascular adipose tissue (cPVAT) has been associated to the burden of cardiovascular risk factors and to the underlying vessel atherosclerotic plaque severity. Although the "outside to inside" hypothesis of PVAT-derived-adipokine regulation of vessel function is currently accepted, whether the resident mesenchymal stem cells (ASCs) in PVAT have a regulatory role on the underlying vascular arterial smooth muscle cells (VSMCs) is not known. Here, we investigated the interactions between resident PVAT-ASCs and VSMCs. ASCs were obtained from PVAT overlying the left anterior descending (LAD) coronary artery of hearts removed at heart transplant operations. PVAT was obtained both from patients with non-ischemic and ischemic heart disease as the cause of heart transplant. ASCs were isolated from PVAT, phenotypically characterized by flow cytometry, functionally tested for proliferation, and differentiation. Crosstalk between ASCs and VSMCs was investigated by co-culture studies. ASCs were detected in the adventitia of the LAD-PVAT showing differentiation capacity and angiogenic potential. ASCs obtained from PVAT of non-ischemic and ischemic hearts showed different tissue factor (TF) expression levels, different VSMCs recruitment capacity through the axis ERK1/2-ETS1 signaling and different angiogenic potential. Induced upregulation of TF in ASCs isolated from ischemic PVAT rescued their angiogenic capacity in subcutaneously implanted plugs in mice, whereas silencing TF in ASCs decreased the proangiogenic capacity of non-ischemic ASCs. The results indicate for the first time a novel mechanism of regulation of VSMCs by PVAT-ASCs in angiogenesis, mediated by TF expression in ASCs. Regulation of TF in ASCs may become a therapeutic intervention to increase cardiac protection.
Keyphrases
- coronary artery
- adipose tissue
- poor prognosis
- mesenchymal stem cells
- cardiovascular risk factors
- coronary artery disease
- signaling pathway
- heart failure
- endothelial cells
- randomized controlled trial
- flow cytometry
- vascular smooth muscle cells
- ischemia reperfusion injury
- cell proliferation
- induced apoptosis
- vascular endothelial growth factor
- mass spectrometry
- oxidative stress
- patient safety
- stem cells
- atrial fibrillation
- high fat diet
- risk assessment
- drug induced
- aortic valve
- long non coding rna
- insulin resistance
- cerebral ischemia
- pi k akt
- cell death
- cell cycle arrest
- risk factors
- angiotensin ii
- skeletal muscle
- cell therapy
- emergency medicine