Vascular remodeling

Research Article

THE INDONESIAN BIOMEDICAL JOURNAL

The Role of Vascular Remodeling and Vascular Repairing in Normoalbuminuria Normotension, Normoalbuminuria Hypertension and Microalbuminuria Hypertension. Focused on Transforming Growth Factor-b1 ( TGF-b1 ) , Matrix Metalloproteinase-9 ( MMP-9 ) and Vascular Endotelial Growth Factor Receptor-2 ( VEGFR-2 )

Background:

Vascular remodeling was an adaptative procedure of the vascular wall that occurred in response to long-run alterations in hemodynamic conditions that contribute to the alterations of the vascular construction and the pathophysiology of vascular disease.

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On the other manus, Endothelial Progenitor Cells ( EPC ) derived from bone marrow had the capacity to migrate to the peripheral circulation and to distinguish into mature endothelial cells. Therefore, EPC could lend in the endothelial repairing after endothelial hurt.

Methods:

This survey was a comparative survey with transverse sectional design. Analysis was done among 30 topics with normoalbuminuria normotension, 55 topics with normoalbuminuria high blood pressure and 30 topics with microalbuminuria high blood pressure. TGF-b1, MMP-9 and VEGFR-2 testing were performed by ELISA method. All statistical computations were performed utilizing the SPSS 11.5 statistical package bundle. We used the Independent sample T trial, Mann-Whitney, One Way Annova and Kruskal Walris to set up the difference among assorted biochemical steps.

Consequences:

TGF-b1 concentration was increased from normotension to normoalbuminuria high blood pressure and to microalbuminuria high blood pressure ( 27631.78 ± 12972.46 Vs 38611.93 ± 17095.46 V 38739.39 ± 12639.11 rg/mL ) . TGF-b1 concentration was higher significantly in normotension as compared to high blood pressure ( p & lt ; 0.001 ) and to microalbuminuria high blood pressure ( p & lt ; 0.001 ) . MMP-9 concentration was increased in normotension to normoalbuminuria high blood pressure but was decreased in microalbuminuria high blood pressure ( 438196.7 ± 156426.8 Vs 564587.3 ± 291287.6 V 418690.0 ± 188380.1 rg/mL ) . MMP-9 concentration was higher significantly in normoalbuminuria high blood pressure as compared to microalbuminuria high blood pressure ( p = 0.028 ) . VEGFR-2 concentration was decreased from normotension to normoalbuminuria high blood pressure and to microalbuminuria high blood pressure ( 9905.52 ± 1851.58 Vs 9395.61 ± 1754.13 V 9005.06 ± 1471.73 rg/mL ) . VEGFR-2 concentration was higher significantly in normotension as compared to microalbuminuria high blood pressure ( p = 0.042 ) .

Conclucions:

The increasing concentration degree of TGF-b1 and diminishing concentration degree of MMP-9 in microalbuminuria high blood pressure showed that the reconstructing procedure was acquiring increased. The diminishing concentration degree of VEGFR-2 in microalbuminuria high blood pressure showed that the mending procedure was acquiring lessening.

Keywords:

Vascular remodeling, Vascular Repairing, TGF-b1, MMP-9, VEGFR-2

Vascular reconstructing in high blood pressure was characterized by a thickened media, a decreased lms, and an increased extracellular matrix. These alterations were associated with endothelial disfunction. Structural alterations in hypertensive vass were associated with increased growing factors: TGF-b1, local vasoactive substances: Ang II, matrix proteins: collagen and elastin, matrix proteases: collagenase and elastase.

Microalbuminuria ( MAU ) which was defined as an unnatural urinary elimination of albumen between 30 and 300 mg/d, was an incorporate marker of cardiovascular hazard and related to the badness of mark organ harm in high blood pressure and besides for placing patients at higher planetary hazard ( Pontremoli ) .

TGF-b regulated the proliferation and distinction of cells, embryologic development, wound mending and angiogenesis. TGF-b besides suppressed the immune system and induces extracellular-matrix constituents. The overrun of TGF-b could ensue in inordinate depostion of extracellular matrix, cicatrix tissue and fibrosis which eventually resulted to the tissue harm ( Blobe ) .

Increased degree of MMP-9 in high blood pressure played an of import function in vascular remodeling and was associated with devastation of the elastic laminae of arterias and aneurysm formation. Recently, MMP-9 degrees had been identified as a fresh forecaster of cardiovascular hazard in patients with coronary arteria disease and shot ( Yasmin ) .

On the other manus, Endothelial Progenitor Cells ( EPCs ) form bone marrow had the capacity to migrate to the peripheral circulation and to distinguish into mature endothelial cells. EPCs were characterized by the look of CD133, CD34, and VEGFR-2. Early EPC in bone marrow or instantly after migration into systemic circulation were positive for CD133/CD34/VEGFR-2. Go arounding EPCs were postitive for CD34/VEGFR-2/CD31/VE-cadherin/von Willebrand factor. The loss of CD133 reflected the transmutation of go arounding EPCs into more mature endothelial-like cells ( Hristov ) .

We hypothesized that in human organic structure, normal homeostasis was required to equilibrate the interactions between reconstructing and mending vascular procedure in high blood pressure. When the balance between reconstructing and mending was perturbed, disease could ensue. The aim of this research was to to find the concentration differences of TGF-b1, MMP-9 and VEGFR-2 among normoalbuminuria normotension, normoalbuminuria high blood pressure and microalbuminuria high blood pressure

Patients and Mehtods

Thirty ( 30 ) topics with normoalbuminuria normotension, with the undermentioned standards: systolic blood force per unit area ( BP ) of & lt ; 139 mmHg and diastolic BP of & lt ; 89 mHg and MAU elimination of & lt ; 30 milligram / milligram creatinine.

Fifty five ( 55 ) topics with normoalbuminuria high blood pressure, with the undermentioned standards: systolic blood force per unit area ( BP ) of & gt ; 140 mmHg and/or diastolic BP of & gt ; 90 mHg and MAU elimination of & lt ; 30 milligram / milligram creatinine.

Thirty ( 30 ) topics with microalbuminuria high blood pressure, with the undermentioned standards: systolic blood force per unit area ( BP ) of & gt ; 140 mmHg and/or diastolic BP of & gt ; 90 mHg and MAU elimination of & gt ; 30 milligram / milligram creatinine.

This survey was a comparative survey with transverse sectional design. All participants gave their informed consent to take part in this survey.

Assaies of Biochemical Markers

Venous blood was collected from all fasting topics and so serum was separated from whole blood after centrifugation and instantly kept at -20?C until measuring. TGF-b1, MMP-9 and VEGFR-2 were determined by ELISA method utilizing assay kit from R & A ; D Systems, USA.

Statistical Anyalysis

Statistical analysis was performed utilizing of SPSS version 11.5 Inc. Chicago. We used the Independent sample T trial, Mann-Whitney, One Way Annova and Kruskal Walris to set up the differences among assorted biochemical steps.

Consequences

The baseline features of the topics were shown in Table 1.

Table 1. Basic Capable Characteristics ( entire 115 patients )

Table 2. Mean degree of TGF-?1, MMP-9 and VEGFR-2 in normoalbuminuria normotension, normoalbuminuria high blood pressure and microalbuminuria high blood pressure

Variable

Normoalbuminuria

Normoalbuminuria

Microalbuminuria

Normotension

High blood pressure

High blood pressure

TGF-?1

27631.78 ± 12972.46

38611.93 ± 17095.46

38739.39 ± 12639.11

MMP-9

438196.7 ± 156426.8

564587.3 ± 291287.6

418690.0 ± 188380.1

VEGFR-2

9905.52 ± 1851.58

9395.61 ± 1754.13

9005.06 ± 1471.73

Table 2 showed that:

1. Concentration of TGF-?1 increased from normoalbuminuria normotension to normoalbuminuria high blood pressure and microalbuminuria high blood pressure

2. Concentration of MMP-9 increased from normoalbuminuria normotension to normoalbuminuria high blood pressure but decreased to microalbuminuria high blood pressure

3. Concentration of VEGFR-2 decreased from normoalbuminuria normotension to normoalbuminuria high blood pressure and microalbuminuria high blood pressure

Table 3. T-test analysis of TGF-?1, MMP-9 and VEGFR-2 in normotention and high blood pressure

Variable

Normotension

High blood pressure

Phosphorus

TGF-?1

27631.78 ± 12972.46

38656.92 ± 15589.50

& lt ; 0.001

MMP-9

438196.7 ± 156426.8

513094.1 ± 267798.3

0.399

VEGFR-2

9905.52 ± 1851.58

9257.77 ± 1661.65

0.078

Table 3 showed that TGF-?1 concentration was increased significantly ( p & lt ; 0.001 ) from normotension to high blood pressure. MMP-9 concentration increased from normotension to high blood pressure but no statictically important. VEGFR-2 concentration decreased from normotension to high blood pressure but non statistically important.

Table 4. T-test analysis of TGF-?1, MMP-9 and VEGFR-2 in normoalbuminuria high blood pressure and microalbuminuria high blood pressure

Variable

Normoalbuminuria

Microalbuminuria

P

High blood pressure

High blood pressure

TGF-?1

38611.93 ± 17095.46

38739.39 ± 12639.11

0.541

MMP-9

564587.3 ± 291287.6

418690.0 ± 188380.1

0.028

VEGFR-2

9395.61 ± 1754.13

9005.06 ± 1471.73

0.443

Table 4 showed that TGF-?1 concentration was increased from normoalbuminuria high blood pressure to microalbuminuria high blood pressure but non statistically important. MMP-9 and VEGFR-2 concentration is decreased from normoalbuminuria high blood pressure to microalbuminuria high blood pressure but non statistically important.

Table 5. T-test analysis of TGF-?1, MMP-9 and VEGFR-2 in normotension and microalbuminuria high blood pressure

Variable

Normotension

Microalbuminuria

P

Normoalbuminuria

High blood pressure

TGF-?1

27631.78 ± 12972.46

38739.39 ± 12639.11

& lt ; 0.001

MMP-9

438196.7 ± 156426.8

418690.0 ± 188380.1

0.664

VEGFR-2

9905.52 ± 1851.58

9005.06 ± 1471.73

0.042

Table 5 showed that TGF-?1 concentration was increased significantly from normoalbuminuria normotension to microalbuminuria high blood pressure ( p & lt ; 0.001 ) . MMP-9 and VEGFR-2 concentration was decreased from normoalbuminuria normotension to microalbuminuria high blood pressure but non statistically important.

Discussions

The instability procedure between reconstructing and mending vascular in high blood pressure was predicted to lend for the stiffness and thickness of vascular wall that eventually would speed up and give high blood pressure complication.

1. Differences of TGF-?1 among normoalbuminuria normotension, normoalbuminuria high blood pressure and microalbuminuria high blood pressure

In this survey, we found that TGF-?1 concentration was increased bit by bit from normoalbuminuria normotension to normoalbuminuria high blood pressure and to microalbuminuria high blood pressure. This indicated that reconstructing procedure was increased every bit good occurred in respond to a long term alterations in hemodynamic status such as increased blood force per unit area that contributed to the pathophysiology of vascular disease and circulatory upsets in the hereafter. Several possibilities which explained this issues because in high blood pressure, the increasing of blood force per unit area had positive correlativity with the polymorphysm of TGF-?1 gen that impacted to the increasing of TGF-?1 degrees. On the other manus, in high blood pressure instances, the increasing of TGF-?1 look in vascular wall would bring on the collagen synthesis in the smooth musculus cell that impacted in conformity to the thickness of vascular wall and eventually would decline the increasing of blood force per unit area.

Based on other research worker findings, August et.al ( 2006 ) found the relationship between TGF-?1 serum with blood force per unit area and the relationship between TGF-?1 polimorphysm gen with high blood pressure topics. The concentration of TGF-?1 plasma was higher comparison to the high blood pressure subjects with microalbuminuria and left ventricle hypertrophy ( LVH ) . This consequences was in conformity with our findings in which we besides found the positive correlativity between TGF-?1 concentration with systolic and diastolic blood force per unit area.

2. Differences of MMP-9 among normoalbuminuria normotension, normoalbuminuria high blood pressure and microalbuminuria high blood pressure

In this survey, we found that MMP-9 concentration was increased from normoalbuminuria normotension to normoalbuminuria high blood pressure but was decreased to microalbuminuria high blood pressure. We found that MMP-9 concentraion had a positive correlativity with systolic and diastolic blood force per unit area.

Long term blood force per unit area increasing would do the accretion of Extra Cellular Matrix ( ECM ) deposits in vascular wall. Increasing of ECM would lend to the patterned advance of LVH and contracting the diameter of artery luminal. MMP-9 had an of import function in the physiology and pathophysiology of remodelling vascular, angiogenesis and arterial sclerosis because MMP-9 had the map to degrade ECM such as collagen type IV and elastin. In this survey, we found that MMP-9 concentration was increased from normoalbuminuria normotension to normoalbuminuria high blood pressure, because in line with the increasing of TGF-?1, MMP-9 increased besides to degrade the excessive of ECM sedimentations. On the other manus, mechanical stretch and shear emphasis would every bit good increased MMP-9 synthesis in VSMC and endothelial cell.

Our latest determination revealed that MMP-9 concentration was lower in microalbuminuria high blood pressure comparison to normoalbuminuria normotension and normoalbuminuria high blood pressure. Some possibilities because the inordinate increased of TGF-?1 inhibited MMP messenger RNA synthesis to give proenzyme ( pro-enzyme of MMP ) . Besides, TIMP, which functioned as MMP inhibitor in commanding ECM metamorphosis, could suppress the ripening of MMP from proenzyme transformed to be active MMP enzyme. Other possibilities, because microalbuminuria which was a biomarker in foretelling vascular disease would impact to the decreasing of MMP-9 look in high blood pressure topics, whereas, MMP-9 should usually move to counterbalance the increasing of ECM. This would heighten the harm of vascular tone.

3. Differences of VEGFR-2 among normoalbuminuria normotension, normoalbuminuria high blood pressure and microalbuminuria high blood pressure

In this survey, we found that VEGFR-2 concentration was decreased from normoalbuminuria normotension to normoalbuminuria high blood pressure and to microalbuminuria high blood pressure. This indicated that high blood pressure could diminish the degree of Endothelial Progenitor Cell ( EPC ) degree. Imanishi at EL. ( 2005 ) found that high blood pressure could speed up EPC aging through the oxidative emphasis and telomerase inactivation. Recently in vitro survey obtained that oxidised LDL and Ang II induced EPC aging through oxidative emphasis. Ang II increased gp91phox look in EPC, which contributed to oxidative emphasis by organizing peroxynitrite, thiobarbituric acid and 8-epiisoprosyanes, which were positive markers for peroxidized lipoid and oxidative emphasis. Telomerase activation had the map to protract life-time and functional activity of endothelial cell.

Decision

The increasing concentration degree of TGF-b1 and diminishing concentration degree of MMP-9 in microalbuminuria high blood pressure showed that reconstructing procedure is acquiring increased. The diminishing concentration degree of VEGFR-2 in microalbuminuria high blood pressure showed that mending procedure is acquiring lessening.

Mentions

Asahara T, MuroharaT, Sullivan A, Silver M, new wave der Zee R, Li T, Witzenbichler B, Schatterman G, Isner JM. 1997. Isolation of putative primogenitor endothelial cells for angiongenesis. Science.275:964-967

August P. , Suthanthiran M. 2006. Transforming growing factor b Signaling, Vascular remodeling, and high blood pressure. N Engl J Med. 354:25

Blobe GC. , Schiemann WP. , Lodish HF. Role of transforming growing factor- B in human disease. N Engl J Med. 2000 ; 342:1350-58

Hristov M. , Erl W. , Weber PC. 2003. Endothelial Progenitor Cells Mobilization, Differentiation and Homing. Arterioscler Thromb Vasc Biol. 23:1185-1189

Imanishi T. , Moriwaki C. , Hano T. , Nishio I. 2005. Endothelial primogenitor cell aging is accelerated in both experimental hypertensive rats and patients with indispensable high blood pressure. J Hypertens. 23:1831-1837.

Imanishi T. , Hano T. , Nishio I. 2005. Angiotensin II accelerates endothelial primogenitor cell aging through initiation of oxidative emphasis. J Hypertens. 23:97-104.

Pontremoli R. et Al, 2002. Microalbuminuria, cardiovascular, and nephritic hazard in Primary Hypertension. J Am Soc Nephrol.13: S169-S172

Yasmin, et Al, 2005. Matrix Metalloproteinase-9 ( MMP-9 ) , MMP-2, and serum elastase activity are associated with systolic high blood pressure and arterial stiffness. Arterioscler Thromb Vasc Biol. 25:3772-378

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