Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension

Whitaker, Morgan; Nair, Vineet; Sinari, Shripad; Dherange, Parinita; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L.; Hemnes, Anna R.; Austin, Eric D.; Patel, Kumar; Black, Stephen M.; Garcia, Joe G.N.; Yuan, Jason X.‐J.; Vanderpool, Rebecca; Rischard, Franz; Bedrick, Edward J.; Desai, Ankit A.

doi:10.1016/j.amjmed.2017.12.046

Cited by 29 publications

(21 citation statements)

References 35 publications

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“…Recently, we also reported that pulmonary arterial stiffness and elasticity are significantly higher in PH patients with DM than in PH patients without DM (Whitaker et al . ). These data suggest that there is a strong association between DM and the progression or severity of PH.…”

Section: Vascular Function In Hyperglycaemiamentioning

confidence: 97%

Pulmonary vascular dysfunction in metabolic syndrome

Willson

Watanabe

Tsuji‐Hosokawa

2018

The Journal of Physiology

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Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function.

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Section: Vascular Function In Hyperglycaemiamentioning

confidence: 97%

Pulmonary vascular dysfunction in metabolic syndrome

Willson

Watanabe

Tsuji‐Hosokawa

2018

The Journal of Physiology

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“…fibrosis, oxidative stress, altered calcium homeostasis and substrate metabolism) [8][9][10]; through indirect effects via alterations in vascular function (e.g. arterial stiffening and microvascular dysfunction) [11]; and (or) through ventricular interdependence (i.e. structure, compliance, and function of the one ventricle, through direct mechanical interaction via septal wall and pericardium, may affect structure and function of the other ventricle) [3][4][5].…”

mentioning

confidence: 99%

Associations of (pre)diabetes with right ventricular and atrial structure and function: the Maastricht Study

Linssen

Veugen

Henry

et al. 2020

Cardiovasc Diabetol

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Backgrounds: The role of right ventricular (RV) and atrial (RA) structure and function, in the increased heart failure risk in (pre)diabetes is incompletely understood. The purpose of this study is to investigate the associations between (pre)diabetes and RV and RA structure and function, and whether these are mediated by left ventricular (LV) alterations or pulmonary pressure. Methods: Participants of the Maastricht Study; a population-based cohort study (426 normal glucose metabolism (NGM), 142 prediabetes, 224 diabetes), underwent two-dimensional and tissue Doppler echocardiography. Multiple linear regression analyses with pairwise comparisons of (pre)diabetes versus NGM, adjusted for cardiovascular risk factors, and mediation analyses were used. Results: In general, differences were small. Nevertheless, in individuals with prediabetes and diabetes compared to NGM; RA volume index was lower (both p < 0.01, p trend < 0.01), RV diameter was lower (both p < 0.01, p trend < 0.01) and RV length was significantly smaller in diabetes (p = 0.67 and p = 0.03 respectively, p trend = 0.04), TDI S′RV was lower (p = 0.08 and p < 0.01 respectively, p trend < 0.01), TDI E′RV was lower (p = 0.01 and p = 0.02 respectively, p trend = 0.01) and TDI A′RV was lower (p < 0.01 and p = 0.07 respectively, p trend = 0.04). Only the differences in RA volume index (7.8%) and RV diameter (6.2%) were mediated by the maximum tricuspid gradient, but no other LV structure and function measurements. Conclusions: (Pre)diabetes is associated with structural RA and RV changes, and impaired RV systolic and diastolic function, independent of cardiovascular risk factors. These associations were largely not mediated by indices of LV structure, LV function or pulmonary pressure. This suggests that (pre)diabetes affects RA and RV structure and function due to direct myocardial involvement.

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“…Although fibrosis may be present in any organ of the body (Gilbert and Cooper, 1999;Patil et al, 2011), its involvement of the cardiovascular system is particularly prevalent in DM. While there may be more subtle processes involving the pulmonary arterial stiffness and cardiac right ventricle in association with pulmonary hypertension (PH) in DM (Grinnan et al, 2016;Whitaker et al, 2018), metabolic dysfunction has been identified in particular (Irwin et al, 2014;Lai et al, 2019). Up to 30% of patients with HFpEF have DM (Piccini et al, 2004).…”

Section: Tg2 In Hyperglycemia Mediated Cardiopulmonary Remodelingmentioning

confidence: 99%

Increased Transglutaminase 2 Expression and Activity in Rodent Models of Obesity/Metabolic Syndrome and Aging

et al. 2020

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Diastolic dysfunction of the heart and decreased compliance of the vasculature and lungs (i.e., increased organ tissue stiffness) are known features of obesity and the metabolic syndrome. Similarly, cardiac diastolic dysfunction is associated with aging. Elevation of the enzyme transglutaminase 2 (TG2) leads to protein cross-linking and enhanced collagen synthesis and participates as a candidate pathway for development of tissue stiffness. With these observations in mind we hypothesized that TG2 may be elevated in tissues of a rat model of obesity/metabolic syndrome (the ZSF 1 rat) and a mouse model of aging, i.e., the senescent SAMP8 mouse. In the experiments reported here, TG2 expression and activity were found for the first time to be spontaneously elevated in organs from both the ZSF1 rat and the SAMP8 mouse. These observations are consistent with a hypothesis that a TG2-related pathway may participate in the known tissue stiffness associated with cardiac diastolic dysfunction in these two rodent models. The potential TG2 pathway needs better correlation with physiologic dysfunction and may eventually provide novel therapeutic insights to improve tissue compliance.

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Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension

Cited by 29 publications

References 35 publications

Pulmonary vascular dysfunction in metabolic syndrome

Pulmonary vascular dysfunction in metabolic syndrome

Associations of (pre)diabetes with right ventricular and atrial structure and function: the Maastricht Study

Increased Transglutaminase 2 Expression and Activity in Rodent Models of Obesity/Metabolic Syndrome and Aging

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