Isabella of Portugal, Holy Roman Empress (d. 1539)
Isabella of Portugal (24 October 1503 – 1 May 1539) was the empress consort and queen consort of her cousin Charles V, Holy Roman Emperor, who was the ruler of the Spanish Empire. She was Queen of Spain and Germany, and Lady of the Netherlands from 10 March 1526 until her death in 1539, and became Holy Roman Empress and Queen of Italy in February 1530. She was the regent of Spain because of her husband's constant travels through Europe, ensuring that the kingdom remained independent of imperial policies and economically healthy during her lifetime.