Adiponectin, Cardiovascular Function, and Hypertension

Hypertension is a major risk factor for cardiovascular disease, and the latter is the leading cause of morbidity and mortality worldwide. In developed countries, hypertension ranks as the top contributing factor for mortality and third in causing disability-adjusted life years. Hypertension is a polygenic and complex disease with rising prevalence. More than 25% of the adult population is affected by hypertension, and two thirds of those individuals reside in developing countries. Europe shows an even higher prevalence of hypertension than North America. With the present trends, the prevalence of hypertension is predicted to increase to 30%, or ~ 1.5 billion people, on the globe in the next 20 years. Mechanistically, endothelial dysfunction, increased renin-angiotensin system (RAS) activity, and sympathetic nervous system (SNS) hyperactivation have been considered as important risk factors of hypertension and hint at important events taking place at the interface of the endothelium, kidney, and SNS.

Obesity is a global epidemic in children and adults. In the United States, a steady increase of the prevalence of obesity has been found in all states. It is estimated that 65% of the population is overweight, which is judged by body mass index of 25.0 to 29.9, and 30% are obese (body mass index of ≥ 30.0). These numbers have been continuously rising in the past 15 years. The National Health and Nutrition Examination Survey III for ~18 000 adults found that body mass index is an associated risk factor for hypertension independent of age, sex, race, and smoking. A long-term weight/hypertension relationship study showed that weight loss of ~ 10 kg is associated with a significant decrease of both diastolic and systolic blood pressure. Obesity and hypertension are 2 complex disorders that are closely interrelated, but the precise underlying association remains elusive.

The uncontrolled expansion of adipose tissue is the key feature of obesity. In the past 2 decades, the view of adipose tissue has gone from revolutionary change from inert energy store to the biggest endocrine organ. Adipose tissue secretes leptin, adiponectin, resistin, visfatin, tumor necrosis factor-α, interleukin-6, etc. In the obese state, the secretion of leptin, resistin, tumor necrosis factor-{alpha}, and interleukin-6 is increased, and these molecules have been shown to be associated with insulin resistance and the progression of inflammation. The only hormone displaying an opposite trend is adiponectin. Adiponectin levels have been positively associated with insulin sensitization, glucose use, β-oxidation, and cardiovascular protection.

Adiponectin may also be involved in the progression of hypertension. On a high-salt diet, Ohashi et al showed that adiponectin-deficient animals display significantly higher systolic blood pressure compared with wild-type control animals independent of insulin resistance. Reconstitution of adiponectin expression by adenoviral infection restored normal blood pressure. Overexpression of adiponectin can also decrease the systolic blood pressure in genetically obese KKAy mice. The association between adiponectin and hypertension is also evident in clinical studies by showing that hypoadiponectinemia is a risk factor for hypertension independent of insulin resistance and diabetes.