P38 MAP Kinase Activity Is Correlated With Angiotensin II Type 1 Receptor Blocker–Induced Left Ventricular Reverse Remodeling in Spontaneously Hypertensive Heart Failure Rats

Liang, Qiangrong; Elson, Andrew; Gerdes, A. Martin

doi:10.1016/j.cardfail.2006.04.006

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…31–34 Interestingly, both 10% stretch and IL-17a at 100 ng/mL induced p38MAP kinase phosphorylation in aortic fibroblasts (Figure 5A–C). Moreover, inhibition of p38 MAP kinase with SB203580 prevented the increase in mRNA for collagens 1a1, 3a1 and 5a1 caused by stretch (Figure 5D–5F).…”

Section: Resultsmentioning

confidence: 97%

Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase

Thabet

Kirabo

et al. 2014

Circulation Research

213

187

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Rationale Aortic stiffening commonly occurs in hypertension and further elevates systolic pressure. Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch and aortic stiffening in hypertension remains undefined. Objective To determine the role of inflammation and mechanical stretch in aortic stiffening. Methods and Results Chronic angiotensin II infusion caused marked aortic adventitial collagen deposition, as quantified by Masson’s Trichrome Blue staining and biochemically by hydroxyproline content, in wild-type (WT) but not in Recombination Activation Gene-1 deficient (RAG-1−/−) mice. Aortic compliance, defined by ex-vivo measurements of stress-strain curves, was reduced by chronic angiotensin II infusion in WT mice (p<0.01) but not in RAG-1−/− mice (p<0.05). Adoptive transfer of T cells to RAG-1−/− mice restored aortic collagen deposition and stiffness to values observed in WT mice. Mice lacking the T cell derived cytokine IL-17a were also protected against aortic stiffening. In additional studies, we found that blood pressure normalization by treatment with hydralazine and hydrochlorothiazide prevented angiotensin II-induced vascular T cell infiltration, aortic stiffening and collagen deposition. Finally, we found that mechanical stretch induces expression of collagen 1α1, 3α1 and 5a1 in cultured aortic fibroblasts in a p38 MAP kinase-dependent fashion, and that inhibition of p38 prevented angiotensin II-induced aortic stiffening in vivo. IL-17a also induced collagen 3a1 expression via activation of p38 MAP kinase. Conclusions Our data define a pathway in which inflammation and mechanical stretch lead to vascular inflammation that promotes collagen deposition. The resultant increase in aortic stiffness likely further worsens systolic hypertension and its attendant end-organ damage.

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Section: Resultsmentioning

confidence: 97%

Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase

Thabet

Kirabo

et al. 2014

Circulation Research

213

187

View full text Add to dashboard Cite

show abstract

“…related kinase (ERK1/2), and c-Jun N-terminal kinase (JNK)]. In animal models of heart failure, activation of MAPK signaling plays a vital role in LV remodeling and treatment with ARBs reduces the activation of MAPK signaling (See et al, 2004;Liang et al, 2006), suggesting that activation of MAPK is mediated through AT 1 receptor. Moreover, Koka et al, demonstrated that treatment with AT 1 receptor blocker or blockade of ERK1/2 or MAPK by either specific inhibitor was able to abolish ANG-II-induced ACE-2 downregulation in human kidney tubular cells, suggesting that ANG-II-induced ACE-2 downregulation is associated with activation of ERK1/2 and p38 MAP kinase pathways (Koka et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Telmisartan acts through the modulation of ACE-2/ANG 1–7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis

et al. 2012

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“…Kumar et al have also shown that losartan does not affect P-p38 levels in isolated rat hearts exposed to ischemia-reperfusion [39], whereas AT2 inhibition by PD123,319 leads to an increase in P-p38 levels [39]. It has been shown that the ARB L-1258, 809 attenuated cardiac p38 activation in spontaneously hypertensive heart failure rats [40]. Thus, different effects of ARBs on p38 activation are seen in different experimental models.…”

Section: Cox2mentioning

confidence: 93%

Additive Effect of TAK-491, a New Angiotensin Receptor Blocker, and Pioglitazone, in Reducing Myocardial Infarct Size

Keyes

Zhang

et al. 2010

Cardiovasc Drugs Ther

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P38 MAP Kinase Activity Is Correlated With Angiotensin II Type 1 Receptor Blocker–Induced Left Ventricular Reverse Remodeling in Spontaneously Hypertensive Heart Failure Rats

Cited by 14 publications

References 42 publications

Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase

Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase

Telmisartan acts through the modulation of ACE-2/ANG 1–7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis

Additive Effect of TAK-491, a New Angiotensin Receptor Blocker, and Pioglitazone, in Reducing Myocardial Infarct Size

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