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Moderately Acidic pH Promotes Angiogenesis: An In Vitro and In Vivo Study
Mohammad Ali Saghiri1, Armen Asatourian2, Steven M Morgano3
1Department of Restorative Dentistry, Rutgers School of Dental Medicine, Newark, New Jersey; Department of Endodontics, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, California.
Introduction:
This study evaluated the effect of different pH values of 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4 on angiogenesis.
Methods:
Endothelial cells were isolated from the mice molar teeth and placed in 42 Matrigel (Corning, NY)-coated wells, which were prepared and divided into 6 groups (n = 7). Synthetic tissue fluid was prepared and divided into 6 parts, and their pH values were adjusted to 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4. A 2-mL volume from each group was diluted in the growth medium at a ratio of 1:3 and used for tubulogenesis assay. Forty-two 6-week-old mice in 6 groups (n = 7) were used for choroidal neovascularization (CNV). A 2-μL volume from each group or saline (control) was delivered by intravitreal injection on the day of laser application and 1 week later. Data on the number of nodes, the total length of the branches, and CNV areas (μm2) were determined using ImageJ software (National Institutes of Health, Bethesda, MD) and analyzed with 1-way analysis of variance and post hoc Tukey tests. The correlation was assessed between the tested variables.
Results:
The number of nodes decreased with changes in pH values as follows: 6.4 > 5.4 > 7.4 > 8.4 > 9.4 > 4.4. The total branch length decreased with pH value changes as follows: 6.4 > 4.4 > 6.4 > 7.4 > 8.4 > 9.4, and the CNV areas decreased with pH value changes as follows: 6.4 > 5.4 > 4.4 > 7.4 > 8.4 > 9.4.
Conclusions:
Moderately acidic pH values (5.4 and 6.4) enhanced angiogenesis, whereas moderately alkaline pH values (8.4 and 9.4) suppressed angiogenesis.
Insights
Moderately acidic pH levels (5.4 and 6.4) promote new blood vessel formation (angiogenesis), while alkaline pH levels (8.4 and 9.4) inhibit it. This study investigated pH effects on endothelial cells and choroidal neovascularization.
Area of Science:
- Biomedical Science
- Cell Biology
- Ophthalmology
Background:
- Angiogenesis is crucial for physiological and pathological processes.
- The influence of pH on angiogenesis is not fully understood.
- This study investigates the impact of varying pH levels on blood vessel formation.
Purpose of the Study:
- To evaluate the effect of different pH values (4.4-9.4) on endothelial cell tubulogenesis.
- To assess the impact of pH on choroidal neovascularization (CNV) in a mouse model.
- To determine the optimal pH range for promoting angiogenesis.
Main Methods:
- Endothelial cells from mouse molar teeth were cultured in Matrigel.
- Tubulogenesis was assessed across pH values ranging from 4.4 to 9.4.
- Choroidal neovascularization (CNV) was induced in mice and treated with varying pH solutions.
Main Results:
- Angiogenesis, measured by node count and branch length, was highest at pH 6.4 and 5.4.
- Choroidal neovascularization areas were smallest at pH 6.4, 5.4, and 4.4.
- Alkaline pH values (8.4 and 9.4) showed reduced angiogenesis compared to neutral pH (7.4).
Conclusions:
- Moderately acidic pH (5.4 and 6.4) significantly enhances angiogenesis.
- Moderately alkaline pH (8.4 and 9.4) suppresses angiogenesis.
- pH is a critical factor influencing blood vessel formation and CNV.
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