Microvascular Function and Endothelial Progenitor Cells in Patients with Severe Hypercholesterolemia and the Familial Hypercholesterolemia Phenotype

Abstract

Objective: To evaluate endothelial progenitor cells (EPCs) and systemic microvascular function in patients with severe hypercholesterolemia, comparing patients with the definite familial hypercholesterolemia (FH) phenotype (DFH) or probable/possible FH phenotype (PFH). There is a large spectrum of atherosclerotic disease between these two clinical phenotypes of FH, and to acquire further knowledge of the pathophysiology of vascular disease in both is desirable. Methods: Subjects with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) >190 mg/dL, were classified as DFH or PFH and underwent measurement of the number of EPCs by flow cytometry and evaluation of cutaneous microvascular reactivity using a laser speckle contrast-imaging system with iontophoresis of acethylcholine (ACh) or sodium nitroprusside. EPCs were defined as CD45- or CD45^low, CD34+CD133+CD309+ cells. Categorical variables were compared using Fisher test and continuous variables with Student t test or Mann-Whitney test, and a value of p < 0.05 was considered statistically significant. Results: Patients with DFH had higher LDL-C than those with PFH. There was no difference in the median number of EPCs between patients with DFH or PFH, but there was a significant reduction of endothelial-dependent, ACh-induced vasodilatation in the former. Conclusion: Patients with DFH have impaired microvascular endothelial-dependent vasodilatation compared to those with PFH, indicating more severe vascular disease in the former.

iPSC-Derived Endothelial Cells Reveals LDLR-Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia

“…The current trend in modeling of human diseases is to collect patient-specific iPSCs from individuals with hereditary pathologies and to elucidate the mechanisms of this pathology at the molecular and cellular levels using relevant cells obtained by iPSC differentiation [23]. Patientspecific iPSC-ECs are broadly used to model various disorders, including pulmonary arterial hypertension, Moyamoya disease, fibrodysplasia ossificans progressiva, Huntington's disease, Kawasaki's disease, type I diabetes mellitus, atrial or ventricular septal defects, pulmonary valve stenosis, cardiomyopathy, calcified aortic valve disease, hemophilia A, diabetic endotheliopathy, Hutchinson-Gilford Progeria Syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and peripheral artery disease [27][28][29][30][31][32].…”

Clinical Potential of Hydrogen Sulfide in Peripheral Arterial Disease

“…MVD is due to EC apoptosis and progressive loss of capillaries, which plays a major role in the development and progression of diabetic complications (diabetic retinopathy, nephropathy, and neuropathy). Patients with familial hypercholesterolemia also feature impaired endothelial-dependent vasodilatation [ 50 ].…”

Preoperative exercise induces endothelial progenitor cell mobilisation in patients undergoing major surgery – A prospective randomised controlled clinical proof-of-concept trial

“…Trial participants from both groups started with similar physical capacity at baseline according to their CPET results quantified by peak _ VO 2 (intervention group (mean [range]) 31.00 mL/min/kg vs. control group (mean [range]) 28.00 mL/min/kg; p ¼ 0.605, twotailed independent samples t-test) and anaerobic threshold (intervention group (mean [range]) 17.14 [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] mL/min/kg vs. control group (mean [range]) 17.00 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] mL/min/kg; p ¼ 0.965, two-tailed independent samples t-test).…”

“…In parts also referring to EPCs, a number of studies have shown the importance of exercise for microvascular health [ 12 , 13 , 14 , 15 , 16 , 17 ]. However, the mechanism of endothelial repair through EPCs and its role for microvascular health is still not fully understood.…”