Obesity and vascular dysfunction

Abstract

One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects.

Effect of body weight loss and normalization on blood pressure in overweight non-obese patients with stage 1 hypertension

“…[15][16][17]61,62 Among the adipose tissue-derived substances, pL has multiple actions that are potentially relevant not only for the control of body fat but also for physiological and pathophysiological cardio-renal regulation. 35,63 Elevated plasma pL level has been associated with hypertension in both lean and overweight/obese hypertensive patients.…”

“…[12][13][14] The progression and persistence of obesity have been associated with a progressive alteration of the function and the structure of the vascular wall, including chronic inflammation, endothelial dysfunction, alteration of vascular tone and reactivity, proliferation of smooth muscle cells, neo-angiogenesis and altered patterns of blood flow regulation with both hypertensive and arteriosclerotic consequences. [15][16][17] Some of the metabolic, endocrinologic and hemodynamic changes associated with obesity and hypertension are partially reversed by BW reduction, which decreases BP in overweight non-obese hypertensive patients. Numerous trials of hypertension treatment have shown that weight loss, whether alone or in combination with antihypertensive drugs, has a beneficial effect on BP control.…”

“…This population deserves special interest because (a) overweight is more prevalent than obesity, 4,8,9 (b) overweight patients are more likely, than obese patients, to achieve and maintain BW reduction/normalization, and (c) overweight patients are less likely to present the structural alterations of the vascular wall that are commonly associated with the progression and persistence of obesity and may sustain elevated BP values. [15][16][17] Given this background, the purpose of this study was to evaluate the effects of a 12-month dietary intervention, aimed at BW loss, on BP levels in overweight non-obese adults with never-treated stage 1 hypertension. Changes in some metabolic and endocrine parameters that are usually altered in obesity-related hypertension were also assessed.…”

Transcriptional Alterations of ET-1 Axis and DNA Damage in Lung Tissue of a Rat Obesity Model

“…Recently, the ET axis has been shown to have a role in the growth and progression of several tumor types, including lung cancer (Bhalla et al, 2009) ET-B receptors, such as lung tumors (Ahme et al, 2000). The rat model used in this study is a valuable model for the study of obesity in humans since it offers many features similar to those of human obesity, such as moderate hypertension, hypertriglyceridemia, and insulin resistance, all features of metabolic syndrome (Stapleton et al, 2008). In this study, the overexpression of ET-1, together with the ET-A and ET-B upregulation, was observed in O AH , in line with previous studies on solid tumors (Nakamuta et al, 1993;Kajima and Nihei, 1995;Nelson et al, 1996;Shankar et al, 1998;Bagnato et al, 1999).…”

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

“…While the above findings clearly suggest some evidence for the "paracrine" role of PVAT [12] , a more vigor experimental approach is still necessary to unequivocally define the role of adipocyte-derived factors. The predominant finding of the inhibitory effect of ADRF on the vascular reactivity appears to argue against the exaggerated vascular reactivity or reduced endothelium-dependent relaxation commonly found to be linked with obesity-associated hypertension or metabolic syndrome [13] . It is worthwhile to mention that periaortic fat tissue has been found to stimulate vascular smooth muscle cells proliferation, a structural characteristics consistent with vascular changes associated with aging and obesity [14] .…”