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PANMINERVA MED 2010;52(Suppl. 1 to No. 2):1-7
Vitamin D concentrations, endothelial progenitor cells,
and cardiovascular risk factors
Our study aimed to establish the association of vitamin D sta-
tus with the level of circulating endothelial progenitor cells
(EPCs) and circulating angiogenic cells (CACs) and to demon-
strate the effect of vitamin D on the level of lipoproteins respon-
sible for increased cardiovascular risk and high blood pres-
sure. 41 healthy adults were selected. EPCs were defined as
CD34+/KDR+ cells, and CACs were defined as cells that
expressed endothelial markers after incubation of mononu-
clear blood cells with endothelial growth factors during 5 days.
We found a positive association between EPCs, CACs and the
level of vitamin D and an inverse correlation between several
subclasses of lipoproteins. The level of vitamin D higher than
40 ng/ml demonstrated a positive effect on regulation of blood
pressure, and there was significant difference in choles-
terol/HDL ratio, very low-density lipoproteins, and triglyc-
erides for groups of subjects with varying levels of vitamin D.
K
EY WORDS
:Endothelial progenitor cells, Vitamin D, cardiovas-
cular risk factors.
T
he purpose of this study was to establish the asso-
ciation of vitamin D status with the level of cir-
culating endothelial progenitor cells (EPCs). Vitamin
D deficiency is a common condition, presentin approx-
imately 30% to 50% of the general population. Low 25-
hydroxyvitamin D levels may have an effect on car-
diovascular health, cancer, and diabetes.1-9
Studies on the connection between ischemic heart
disease, hypertension and vitamin D are conflicting.
Some studies found an inverse relationship between
levels of the active form of vitamin D, blood pressure,
and plasma renin activity. 10, 11 Another study report-
ed a positive association.12
Because the vitamin D receptor (VDR) is present in
most cells, vitamin D has a wide rangeof therapeutic
and health-related benefits. The active form of vitamin
D3 is a steroid hormone shown to regulate more than
60 genes.13,14 The translocation of 1α,25(OH)2D3 into
cells, where it binds with high affinity to vitamin D
nuclear receptors, results in altering rates of gene
expression. By this pathway, the active form of vitamin
D influences a number of genes relevant to arterial
wall functions. These include VEGF, matrix metallo-
proteinase, myosin, and structural proteins. Vitamin D
receptors are densely distributed in theendothelium,
and vitamin D3modulates vasculartone by reducing
calcium influx into the endothelial cells. 1,25(OH)2D
is a veryeffective modulator of the immune system. In
animal models, it has been demonstrated that pre-
treatment with 1,25(OH)2Dis effective in preventing
the onset of type 1 diabetes, multiple sclerosis, rheuma-
toid arthritis,and Crohn’s disease.15
Our goal was to prove that optimal levels of vitamin
D could be correlated with the increased number of cir-
culating EPCs and angiogenic cells. The number of
1Center for the Improvement
of Human Functioning International, Inc.
Bio-communication Research Institute Division
Wichita, KS, USA
2Irvine3 Vascular Labs, CH-PE University, Pescara, Italy
Acknowledgments.—This research was supported in part by Allan P.
Markin.
Corresponding author: N. A. Mikirova, PhD, Center for the Improvement
Human Functioning International, Inc., Bio-communication Research
Institute Division, 3100 N. Hillside, Wichita, KS 67219, USA.
E-mail: nmikirova@brightspot.org
N. A. MIKIROVA 1, G. BELCARO2, J. A. JACKSON 1, N. H. RIORDAN 1
Vol. 52 - Suppl. 1 to No. 2 PANMINERVA MEDICA 1
MIKIROVA VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS
2PANMINERVA MEDICA June 2010
circulating EPCs in an individual’s blood may be an
indicator of overall vascular health. In atherosclerosis,
the endothelial layers may become damaged, and near-
by endothelial cells are recruited to help repair vessels
or form new ones. EPCs are generated from bone mar-
row and contribute to repair of the endothelium. A
lack of EPCs can lead to vascular dysfunction and a
progression of atherosclerosis. There are no systematic
studies regarding the physiological variation in the
number or the lifetime of EPCs in physiological or
pathological conditions.16 The effect of cardiovascu-
lar risk factors, diabetes, acute myocardial infarction
and vascular trauma on the number of EPCs has been
described in several studies.17-21 In a large popula-
tion–based study it was shown that there was a posi-
tive relation between EPC numbers and vascular risk
factors and a positive association of EPCs with
Framingham risk factors.22
Our focus was to evaluate if the population of EPCs
could be correlated with vitamin D status. The levels
of EPCs and the level of angiogenic cells developed
from PBMSc in vitro were measured and compared
with the level of vitamin D in serum.
Materials and methods
Study population and methods
Forty-one adults ages 23-74 were included.
Exclusion criteria were hypertension (use of anti-
hypertensive therapy), diabetes mellitus, and a histo-
ry of neoplasm or active cancer. The study was
approved by the Institutional Review Board commit-
tee, and informed consent was obtained from all sub-
jects. Fasting serum and blood samples were taken
and analyzed within 4 hours of collection. The serum
was used for measurements of the lipid profile (total
cholesterol, high-density lipoprotein cholesterol (HDL),
low-density lipoproteins (LDL), triglycerides, very
low-density lipoproteins [VLDV]), glucose, and C-
reactive protein by established clinical laboratory tests.
Blood pressure was measured for each participant on
the same day. Serum level of vitamin D (25(OH)D) was
determined by radioimmunoassay (RIA kit, DiaSorin,
Stillwater, MN). Blood circulating progenitor cells
were phenotyped and quantified by flow cytometric
analysis. Blood collection was taken at the same time
(8-10 a.m.), as there are indications that the number of
EPCs exhibit diurnal variations with an increase
between 3 pm and 10 p.m.22 All participants were
asked to stop taking vitamin D at least one week before
blood drawing.
Method of measurements of endothelial progenitor
cells
EPCs have been identified as a circulating cell pop-
ulation in peripheral blood that co-expresses
hematopoietic stem/progenitor cell markers (CD34 or
AC133) as well as endothelial markers (VE-Cadherin
or VEGFR-2). These cells may augment the injury-
repair process and promote angiogenesis.23, 24
The level of peripheral blood progenitor cells was
analyzed by the expression of cell-surface antigens
with direct 2-color cytometric analysis using fluores-
cein isothiocyanate (FITC)-conjugated and phyco-
erythrin (PE)-conjugated monoclonal antibodies
(mAbs). To measure EPCs, the peripheral blood
mononuclear cells were isolated from peripheral blood
using density-gradient centrifugation. Separated
mononuclear cells were labeled for 20 to 30 min at
4°C using manufacturer-recommended concentrations
with antihuman-KDR-PE (Becton Dickinson, San
Diego, California) and antihuman-CD34-FITC
(Miltenyi Biotec, Auburn, CA, USA). Fluorescent iso-
type-matched antibodies were used as controls. Cell
fluorescence was measured immediately after staining.
A morphological gate included lymphocytes and
monocytes. Circulating EPCs were defined as CD34+/
KDR+ cells.
Method of measurement of angiogenic cells
In addition to the population of circulating EPCs
defined by a specific stem/progenitor cells marker, we
measured the level of angiogenic cells after culturing
mononuclear cells on fibronectin in an endothelial
medium. This cell population was defined as circu-
lating angiogenic cells (CACs)25, 26 and expresses
monocyte/macrophage markers and markers of
endothelial cells. The population includes endothelial
cells, endothelial progenitor cells and cells-expressed
monocyte /macrophage markers. To find the number
of CACs, mononuclear cells were plated in an EBM-
2 medium supplemented with endothelial growth fac-
tors on fibronectin-coated 6-well plates for 5 days.
Adherent cells were detached and stained for markers
of endothelial cells: KDR, CD144, CD105, and
CD62E. In addition, a portion of the cells was incu-
Vol. 52 - Suppl. 1 to No. 2 PANMINERVA MEDICA 3
VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS MIKIROVA
bated with Dil-labeled acLDL (Molecular probe) and
with FITC-labeled Ulex europaeus agglutinin I (ulex-
lectin, Sigma). Morphological analysis of these cells
after 5 days of culture of the mononuclear cells demon-
strated that some cells developed elongated, spindle-
shaped and fibroblast-like morphology after adhesion
to the plate.
Statistical analysis
The data were analyzed by Systat software (Systat,
Inc) and Kaleidagraph software. Variables were pre-
sented as mean values ± SD, or as medians with cor-
responding 25th percentiles. Association of EPCs with
the level of vitamin D and vascular risk factors was
assessed using linear models. Statistical significance
was accepted if the null hypothesis could be rejected
at P≤0.05.
Results
Positive correlation of EPCs, angiogenic cells, and
vitamin D
The study sample was a representation of the healthy
general population. Baseline characteristics of partic-
ipants are shown in Table I (average, minimal, and
maximal values of the age and clinical tests). The mean
25(OH)D concentration for all participants was 29.8
ng/mL. The percentage of participants with a level of
vitamin D less than 20 ng/mL, which is considered
deficient, was 36%. A plasma level of vitamin D in
the range 20-30 ng/mL was considered as insufficient,
and sufficient levels were greater than 30-40 ng/mL.
Optimal levels are between 40-80 ng/mL. Other para-
meters included in Table I are conventional cardio-
vascular risk factors and the level of glucose.
The effect of vitamin D status and risk factors on the
number of circulating EPCs and cultured angiogenic
cells was analyzed for all study subjects. The number
of EPCs measured in circulation was determined as
CD34+/ KDR+ cells. The mean number of EPCs in
PBMCs in the gating area that excluded granulocytes
was (0.05±0.03%). To prove that vitamin D had an
effect on the level of endothelial progenitor cells in
circulation, the values of measured CD34/KDR pos-
itive cells were compared for subjects with a level of
vitamin D higher and lower than sufficient levels.
The distributions of EPCs for the levels of vitamin
D higher and lower than 40 ng/mL are shown in Figure
1. The mean percentage of EPCs for subjects with a lev-
el of vitamin D lower than 40 ng/mL was significant-
ly different than the mean percentage of EPCs for sub-
jects with a level of vitamin D higher than 40 ng/mL
(0.045 versus 0.068, P value for trend <0.01). Mean val-
ues of EPCs for the levels of vitamin D less or higher
than 30 ng/mL were 0.046 and 0.060 respectively
(P<0.05).
A positive correlation was found between CACs
and the level of vitamin D. For development of CACs,
mononuclear cells were placed on fibronectin-coated
plates in a medium with several growth factors: vas-
TABLE I.—Participants’characteristics.
Average Min Max Units
Age 49.65 20 76
Cholesterol 205.56 141 277 mg/dL
Cholesterol/HDL Ratio 3.58 2 6.3
LDL 114.05 47 164 mg/dL
CRP 3.15 0.11 16.63 mg/L
Glucose 100.73 79 198 mg/dL
HDL Cholesterol 62.12 35 124 mg/dL
LDL/HDL Ratio 2.00 0.9 3.6
Triglycerides 143.26 48 457 mg/dL
Vitamin D 29.82 6 60 ng/mL
VLDL 27.1 10 60 mg/dL
Systolic pressure 123.90 92 158 mmHg
Diastolic pressure 73.85 58 96 mmHg
0.12
0.1
0.08
0.06
0.04
0.02
0
0.02
Percentage
Distribution of EPCs for levels of vitaminaD
lower and higher than <10 ng/mL
Vitamin D <40 ng/mL Vitamin ≥40 ng/mL
Figure 1.—Distribution of EPCs for the levels of vitamin D lower and
higher than 40 ng/mL. Each box encloses 50% of data with the median value
of the variable.
MIKIROVA VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS
4PANMINERVA MEDICA June 2010
cular endothelial growth factor (VEGF), fibroblast
growth factor (FGF), epidermal growth factor (EGF)
and insulin-like growth factor (IGF). After 5 days of
exposure to growth factors, attached cells were ana-
lyzed for the presence of endothelial markers. The
angiogenic origin of cultured cells was demonstrated
by expression of VEGF R2 (KDR), CD105, CD62E
and CD144. The expression of these endothelial mark-
er proteins on adherent cells was measured by flow
cytometry. In addition, cells were double stained by
Dil- ac-LDL and lectin. Most of the cells from the
population of attached cells were positive for endothe-
lial markers. The percentage of KDR, CD105, and
CD62E –positive cells was 50% -100% in the gated
region, which included large elongated cells, and 15%-
50% in all attached cells. The expression of CD144 was
lower than 10% for all measured samples.
Because these types of cells participate in vascular
repair and angiogenesis, we further characterized the
effect of vitamin D on the ability of cultured mononu-
clear cells to differentiate to angiogenic cells. The per-
centage of cells differentiated in angiogenic cells in a
medium with endothelial growth factors was com-
pared with the measured levels of vitamin D in the
blood for all participants. The number of CACs demon-
strated a positive association with the level of vitamin
D. Percentage of the total attached cells expressing
KDR was 21% and 34% for the levels of vitamin D less
and higher than 40 ng/mL (P<0.05). For the cells count-
ed in the gated region of 10-14 uM size cells, these
values were 74% (vitamin D < 40 ng/mL) and 89%
(vitamin D? 40ng/ml) with P<0.02.
The same results were found for the population of
cells expressing CD105 and CD62E. The percentage
of cells stained positive for CD62E was 72% for lev-
els of vitamin D less than 40ng/mL, and 89% for lev-
els of vitamin D higher than 40ng/ml. Mean percent-
age of CD105 positive cells from attached cell popu-
lation was increased from 77% to 95% for subjects
with an insufficient or deficient level of vitamin D in
comparison to the subjects with a sufficient level of vit-
amin D. In addition, cultured cells were double stained
by Dil-Ac-LDL and lectin and showed that 50%±24%
of attached cells were stained positive.
Factors that have an inverse correlation with the num-
ber of circulating endothelial progenitor cells
After characterization of the endothelial progeni-
tor cells by expression of CD34 and VEGF receptor
(KDR), the percentage of these cells in circulation
was compared with all other measured parameters:
lipid profile, C-reactive protein, level of fasting glucose,
and blood pressure. We first investigated whether there
was a correlation between the level of EPCs in blood
and the level of several subclasses of lipoproteins. For
many subclasses of lipoproteins, clinical tests gener-
ally focus on the following types: high-density lipopro-
teins (HDL), which transport cholesterol away from
arteries and are protective; low-density lipoproteins
(LDL), which can penetrate the arterial wall and deposit
cholesterol within the artery, thus contributing to heart
disease; and very-low-density lipoproteins (VLDL),
TABLE II.—Average values of EPCs for the levels of test parameters higher and lower than the risk levels.
Parameter Test values lower Percentage Test values higher Percentage P for trend
than borderline of EPCs than borderline of EPCs (one-sided)
Glucose <100mg/dL 0.061 >100 mg/dL 0.044 0.020
VLDL <30 mg/dL 0.061 >30 mg/dL 0.035 0.001
Systolic pressure <140 mmHg 0.060>140 mmHg 0.0400.010
Diastolic pressure <80 mmHg 0.058 >80 mmHg 0.043 0.020
C-reactive protein <5 mg/L 0.055 >5 mg/L 0.047 0.2 (NS)
Cholesterol/HDL < 4.5 0.059 >4.5 0.049 0.2 (NS)
TABLE III.—The average values of clinical tests for subjects with suf-
ficient and insufficient or deficient levels of vitamin D.
Serum 25-OH vitamin D levels
Clinical tests <40 ng/mL ≥40 ng/mL P for trend
(one-sided)
VLDL 31.2 18.7 0.002
Systolic blood pressure 127 115.8 0.030
Diastolic blood pressure 76.6 66.4 0.003
Cholesterol/HDL ratio 3.7 3.0 0.020
Triglycerides 162 110 0.050
C-reactive protein 2.7 1.7 0.080
(NS)
Vol. 52 - Suppl. 1 to No. 2 PANMINERVA MEDICA 5
VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS MIKIROVA
which are similar to LDLs but can more easily pene-
trate the artery wall. Data of inverse correlation of risk
factors with EPCs are shown in Table II.
Data in Table II show the mean percentage of EPCs
for levels of risk factors higher and lower than the
upper border of the normal range and p-values for
trend. For all parameters except C reactive protein,
borderlines for risk factors are chosen as the highest
level of normal range (mean + 2SD) previously esti-
mated in our clinical laboratory. For CRP the level of
borderline equals 5 mg/L and marks the level of high
risk of cardiovascular disease. The average percentages
of EPCs for levels of risk factors higher and lower
than the highest level of normal range are presented in
Table II and show a significant difference in the level
of EPCs for the level of fasting glucose,VLDL, and
blood pressure.
Distributions of the percentage of endothelial prog-
enitor cells in groups of subjects with levels of glu-
cose, VLDL, and systolic pressure higher or lower
than upper borderline of normal range are presented
in Figure 2.
According to our data, there was an inverse corre-
lation between indicated levels of risk factors and the
number of endothelial progenitor cells in circulation,
and a trend towards a lower level of EPCs for subjects
with an increased level of fasting glucose,VLDL, and
blood pressure. For a VLDL level less than 30 mg/dL,
the average value for the percentage of EPCs in cir-
culation was 0.061%, and for VLDL higher than 30
mg/dL the mean value of EPCs was 0.035% (P<0.001).
The inverse association was also found between the
fasting level of glucose and the level of EPCs (0.060%
for the level of glucose less than 100 mg/dL, and
0.044% for the level of glucose higher than 100 mg/dL,
P<0.02). According to the linear correlation analysis,
there was statistically significant inverse correlation
between the level of EPCs and the level of glucose
(P<0.05) and VLDL (P<0.01).
The mean level of EPCs was decreased from 0.06%
for the levels of systolic pressure less than 140 mmHg
to 0.044% for systolic pressure greater than 140 mmHg
(P<0.01). Diastolic pressure mean values of EPCs
were decreased from 0.058% to 0.043% for borderline
pressure 80 mmHg (P<0.02). According to these
results, increased blood pressure was related to a
decreased number of endothelial progenitor cells, and
participants with increased blood pressure had the
reduced number of EPCs in circulation.
The comparison of the levels of C-reactive protein
with the measured level of EPCs for all participants
demonstrated that for a level of CRP higher than 5,
the mean number of endothelial progenitor cells was
decreased from 0.055% to 0.047%, but the difference
was not statistically significant.
Finally, there was an inverse association between
the levels of several risk factors and the EPC number,
and the percentage of circulating CD34+KDR+
endothelial progenitor cells was decreased with
increased values of blood tests, which are indicators of
the occurrence of cardiovascular events or diabetes.
Serum vitamin D inversely correlated with the level of
lipoproteins responsible for the increased cardio-
vascular risk and the level of blood pressure
Because vitamin D may play a role in blood pressure
regulation and vitamin D deficiency may alter the
effects of risk factors, we examined the association
between vitamin D status and cardiovascular risk fac-
tors. The values of cholesterol/HDL ratio, triglyc-
erides, very-low density lipoproteins, C-reactive pro-
tein, and blood pressure averaged for subjects with a
level of vitamin D higher and lower than 40ng/mL are
0.12
0.1
0.08
0.06
0.04
0.02
0
0.02
Percentage
Distribution of EPCs for different levels
of glucose, VLDL and systolic pressure
VLDL
<30 mg/dL
°
VLDL
≥30 mg/dL
Glucose
<100 mg/dL
Glucose
≥100 mg/dL
Systolic
<140 mg/dL
Systolic
≥140 mg/dL
Figure 2.—Percentage of circulating EPCs in subjects with higher and
lower than high borderline of normal range levels of glucose,VLDL, and
systolic pressure.
MIKIROVA VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS
6PANMINERVA MEDICA June 2010
presented in Table III. For a vitamin D level higher
than 40ng/mL, there was a decrease in diastolic pres-
sure (76.6 for vitamin D levels less than 40 ng/mL
and 66.4 for vitamin D levels higher than 40 ng/mL,
P<0.003). For systolic pressure, there was also a
decrease in values from 127 to 115.8 with P for trend
0.03 for subjects with a sufficient level of vitamin D in
comparison with subjects with an insufficient or defi-
cient level of vitamin D.
Vitamin D levels were inversely correlated with the
level of lipoproteins responsible for the increased car-
diovascular risk. There was an inverse relationship
between the levels of vitamin D and cholesterol to
HDL ratio. This factor is considered as a marker of
cardiovascular disease with the average risk factor in
the range between 3.4 and 5.0. Subjects with suffi-
cient vitamin D status (?40 ng/mL) showed reduction
of this parameter from average value 3.7 to 3.0
(P<0.02). Vitamin D deficiency was associated with
increased level of VLDL (31.2 mg/dL versus 18.7
mg/dL, P<0.002).
The increased level of CRP is considered a risk fac-
tor of cardiovascular disease. Mean values of CRP for
the ranges of vitamin D higher and lower than 40
ng/mL were 1.7 and 2.7 (P value for trend 0.08).
Discussion
This study indicates that vitamin D status has an
effect on the number of EPCs in circulation and on
the ability of peripheral mononuclear cells to differ-
entiate in angiogenic cells. Mean values of EPCs for
subjects with a sufficient level of vitamin D (30-40
ng/mL) were higher than for subjects with an insuffi-
cient or deficient level of vitamin D (0.069 versus
0.045, P<0.01). The number of circulating angiogenic
cells developed from the peripheral mononuclear cells
was higher in subjects with a higher level of vitamin
D in the blood.
The possible explanation for these results may be that
the vitamin D hormone is a developmental hormone.
A higher level of vitamin D in circulation and genet-
ic variations in response to vitamin D may have an
impact on the ability of stem cells in circulation to
differentiate in endothelial phenotype. This possibil-
ity is supported by a study in which it was shown that
1,25(OH)2D3 may regulate phospholipase C produc-
tion by the cells, which in turn may modulate signal
transduction by receptors with tyrosine kinase activi-
ty, including VEGF-R1 and VEGF-R2 27 Another study
has shown that vitamin D has an effect on the prolif-
eration of stem cells (human bone-marrow derived
CD34+ and human peripheral blood-derived CD133+
cells).28 Our data of increased level of circulating EPCs
in subjects with a sufficient level of vitamin D may
be explained by the ability of vitamin D to modulate
the number of stem cells and differentiate these cells
in progenitor phenotype.27-29
An increased number of CACs in subjects with a
sufficient level of vitamin D may be explained by the
fact that during angiogenic cell development growth
factors presented in medium could modulate the
expression of the nuclear vitamin D receptors, pre-
sented in several subpopulations of mononuclear cells,
which will contribute to the development of angio-
genic types of cells.
Our study supported results of other studies that
demonstrated that risk factors of cardiovascular disease
and diabetes have an inverse correlation with the num-
ber of circulating EPCs.16, 17, 30 Cardiovascular risk
factors induce endothelial injury and a cascade of pro-
inflammatory events, resulting in the infiltration of
monocytic cells and smooth muscle cells prolifera-
tion, which leads to the formation of atherosclerotic
lesions. EPCs incorporate into the sites of neovascu-
larization and provide endothelial repair. However,
continued exposure to cardiovascular risk factors not
only damages the endothelial layer but may also lead
to depletion of EPCs.
In this study, we compared the levels of EPCs with
risk factors. Our data demonstrated that there is an
association between increased blood pressure and the
level of circulating EPCs. The percentage of EPCs
was decreased from 0.06 to 0.04 for populations with
a level of systolic pressure higher than 140 mmHg
(P<0.01). An increased level of diastolic pressure had
an inverse association with the number of EPCs (0.058
for diastolic pressure less that 80 mm Hg and 0.043 for
diastolic pressure higher than 80 mmHg, P<0.02). The
same tendency was found for the cholesterol/HDL
ratio, concentration of very-low density lipoproteins,
and increased level of fasting glucose. The mecha-
nism by which risk factors may affect EPCs has been
suggested in studies in which it was hypothesized that
progenitor cells are more sensitive to apoptosis induc-
tion.17, 31
The difference between two groups of subjects with
sufficient and insufficient or deficient levels of vitamin
Vol. 52 - Suppl. 1 to No. 2 PANMINERVA MEDICA 7
VITAMIN D CONCENTRATIONS, ENDOTHELIAL PROGENITOR CELLS,AND CARDIOVASCULAR RISK FACTORS MIKIROVA
D was significant for cholesterol/HDL ratio, VLDL,
triglycerides, and blood pressure. A level of vitamin D
higher than borderline 40 ng/mL demonstrated a pos-
itive effect on blood pressure. While it is clear that
vitamin D plays some role in the regulation of blood
pressure, the mechanism of these complex relation-
ships must be evaluated.
Blood vessels and the heart have large numbers of
vitamin D receptors, which means that vitamin D is
providing some function in regulating these tissues.
Laboratory studies have found that vitamin D sup-
presses the activity of the hormone renin, high levels
of which can cause raised blood pressure.32
To maximize health and reduce the risk of common
diseases, it is important to pay attention to the 25(OH)D
concentrations. Maintaining a healthy 25(OH)D con-
centration may be important to prevent coronary dis-
ease. According to our results, the minimum concen-
tration of 25(OH)D should be 40 ng/mL; and for max-
imum bone health and prevention of many chronic
diseases, the vitamin D concentration should be high-
er than 40 ng/mL. Larger clinical trials evaluating
nutritional, environmental and population factors may
better define the possible roles of vitamin D levels in
cardiovascular prevention.
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