The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model
Histamine is a basic amine stored in mast cells, with its release capable of activating one of four histamine receptors. The histamine 3 receptor (H<sub>3</sub>R) is known to be cardioprotective during acute ischemia by acting to limit norepinephrine release. However, a recent study repo...
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2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9757 |
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| author | Samuel L. McCaffrey Grace Lim Martyn Bullock Ainsley O. Kasparian Roderick Clifton-Bligh William B. Campbell Alexander Widiapradja Scott P. Levick |
| author_facet | Samuel L. McCaffrey Grace Lim Martyn Bullock Ainsley O. Kasparian Roderick Clifton-Bligh William B. Campbell Alexander Widiapradja Scott P. Levick |
| author_sort | Samuel L. McCaffrey |
| collection | DOAJ |
| description | Histamine is a basic amine stored in mast cells, with its release capable of activating one of four histamine receptors. The histamine 3 receptor (H<sub>3</sub>R) is known to be cardioprotective during acute ischemia by acting to limit norepinephrine release. However, a recent study reported that myofibroblasts isolated from the infarct zone of rat hearts responded to H<sub>3</sub>R activation by up-regulating collagen production. Thus, it is necessary to clarify the potential role of the H<sub>3</sub>R in relation to fibrosis in the heart. We identified that the mouse left ventricle (LV) expresses the H<sub>3</sub>R. Isolation of mouse cardiac fibroblasts determined that while angiotensin II (Ang II) increased levels of the H<sub>3</sub>R, these cells did not produce excess collagen in response to H<sub>3</sub>R activation. Using the Ang II mouse model of adverse cardiac remodeling, we found that while H<sub>3</sub>R blockade had little effect on cardiac fibrosis, activation of the H<sub>3</sub>R reduced cardiac fibrosis and macrophage infiltration. These findings suggest that when activated, the H<sub>3</sub>R is anti-inflammatory and anti-fibrotic in the mouse heart and may be a promising target for protecting against cardiac fibrosis. |
| first_indexed | 2024-03-10T13:53:50Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:53:50Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fc9177052da44e88acd4affb11e98a152023-11-21T01:53:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124975710.3390/ijms21249757The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse ModelSamuel L. McCaffrey0Grace Lim1Martyn Bullock2Ainsley O. Kasparian3Roderick Clifton-Bligh4William B. Campbell5Alexander Widiapradja6Scott P. Levick7Kolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USAKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaKolling Institute for Medical Research, Royal North Shore Hospital, St Leonards, NSW 2064, AustraliaHistamine is a basic amine stored in mast cells, with its release capable of activating one of four histamine receptors. The histamine 3 receptor (H<sub>3</sub>R) is known to be cardioprotective during acute ischemia by acting to limit norepinephrine release. However, a recent study reported that myofibroblasts isolated from the infarct zone of rat hearts responded to H<sub>3</sub>R activation by up-regulating collagen production. Thus, it is necessary to clarify the potential role of the H<sub>3</sub>R in relation to fibrosis in the heart. We identified that the mouse left ventricle (LV) expresses the H<sub>3</sub>R. Isolation of mouse cardiac fibroblasts determined that while angiotensin II (Ang II) increased levels of the H<sub>3</sub>R, these cells did not produce excess collagen in response to H<sub>3</sub>R activation. Using the Ang II mouse model of adverse cardiac remodeling, we found that while H<sub>3</sub>R blockade had little effect on cardiac fibrosis, activation of the H<sub>3</sub>R reduced cardiac fibrosis and macrophage infiltration. These findings suggest that when activated, the H<sub>3</sub>R is anti-inflammatory and anti-fibrotic in the mouse heart and may be a promising target for protecting against cardiac fibrosis.https://www.mdpi.com/1422-0067/21/24/9757mast cellmacrophagefibroblastimetitA331440histamine receptor agonist |
| spellingShingle | Samuel L. McCaffrey Grace Lim Martyn Bullock Ainsley O. Kasparian Roderick Clifton-Bligh William B. Campbell Alexander Widiapradja Scott P. Levick The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model International Journal of Molecular Sciences mast cell macrophage fibroblast imetit A331440 histamine receptor agonist |
| title | The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model |
| title_full | The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model |
| title_fullStr | The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model |
| title_full_unstemmed | The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model |
| title_short | The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model |
| title_sort | histamine 3 receptor is expressed in the heart and its activation opposes adverse cardiac remodeling in the angiotensin ii mouse model |
| topic | mast cell macrophage fibroblast imetit A331440 histamine receptor agonist |
| url | https://www.mdpi.com/1422-0067/21/24/9757 |
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